Pathogen Genomics and Host
Cellular Susceptibility Factors of COVID-19
Fengyu
Zhang, Michael D. Waters
December 14, 2020
ABSTRACT
Coronavirus
disease 19 (COVID-19) caused by infection with a novel severe acute respiratory
syndrome virus -2 (SARS-CoV2) has evolved into a pandemic and a global public
health emergency. The viral genomics, host cellular factors, and interactions
are critical for establishing a viral infection and developing a related
disease. This paper aims to provide an overview of viral genomics and discuss
host cellular factors so far identified to be involved with the disease
susceptibility. The novel pathogen is a beta coronavirus and one of seven that
cause diseases to humans. It is a single strand positive-sense RNA genome virus
that encodes 27 proteins, including the structural Spike protein that binds to
host cell surface receptors and is a key for viral entry, and 16 nonstructural
proteins play a critical role in viral replication and virulence. While the
angiotensin-converting enzyme, ACE2 receptor, and the proteases TMPRSS2 and
furin are established as necessary for viral entry, host factors CD147,
Cathepsins, DPP4, GRP78, L-SIGN, DC-SIGN, Sialic acid, and Plasmin(ogen) may
also play a role in the viral entry. The Spike protein and nonstructural
proteins, and various host factors working together may contribute to the
infection kinetics, high infectivity, rapid transmission, and a spectrum of
clinical manifestations of COVID-19. More importantly, they can serve as
potential targets in developing strategies for therapeutical prevention and
intervention.
KEYWORDS
SARS-CoV-2,
genomics and genetics, viral-host interaction, susceptibility, COVID-19
Copyright©2020
by Global Clinical and Translational Research.
How to cite this article:
Zhang F and Waters M. Pathogen Genomics and Host cellular
Susceptibility Factors. Glob Clin Transl Res. 2020; 2 (4): 107-126.
DOI:10.36316/gcatr.02.0037
REFERENCES
1.
Zhang X, Tan Y,
Ling Y, Lu G, Liu F, Yi Z, et al. Viral and host factors related to the
clinical outcome of COVID-19. Nature. 2020;583(7816):437-40.
2.
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et
al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J
Med. 2020;382(18):1708-20.
3.
Zhou P, Yang X, Wang X, Hu B, Zhang L, Zhang W, et
al. A pneumonia outbreak associated with a new coronavirus of probable bat
origin. Nature. 2020;579(7798):270-3.
4.
Kim J, Chung Y, Jo H, Lee N, Kim M, Woo S, et al.
Identification of Coronavirus Isolated from a Patient in Korea with COVID-19.
Osong Public Health Res Perspect. 2020;11(1):3-7.
5.
Kojima A, Fujinami F, Doi K, Yasoshima A, Okaniwa
A. Isolation and properties of sialodacryoadenitis virus of rats. Jikken
Dobutsu. 1980;29(4):409-18.
6.
Vijgen L, Keyaerts E, Lemey P, Maes P, Van Reeth
K, Nauwynck H, et al. Evolutionary history of the closely related group 2
coronaviruses: porcine hemagglutinating encephalomyelitis virus, bovine
coronavirus, and human coronavirus OC43. J Virol. 2006;80(14):7270-4.
7.
Stout AE, Andre NM, Jaimes JA, Millet JK, Whittaker
GR. Coronaviruses in cats and other companion animals: Where does
SARS-CoV-2/COVID-19 fit? Vet Microbiol. 2020; 247: 108777.
8.
Zhang Q, Zhang H, Huang K, Yang Y, Hui X, Gao J,
et al. SARS-CoV-2 neutralizing serum antibodies in cats: a serological investigation.
BioRxiv. 2020;doi: https://doi.org/10.1101/2020.04.01.021196.
9.
Fung TS, Liu DX. Human Coronavirus: Host-Pathogen
Interaction. Annu Rev Microbiol. 2019;73:529-57.
10.
Fan Y, Zhao K, Shi Z-L, Zhou P. Bat coronaviruses
in China. Viruses. 2019;11(3):210.
11.
Woo PC, Lau SK, Lam CS, Lau CC, Tsang AK, Lau JH,
et al. Discovery of seven novel Mammalian and avian corona-viruses in the genus
deltacoronavirus supports bat corona-viruses as the gene source of
alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source
of gammacoronavirus and deltacoronavirus. J Virol. 2012;86(7):3995-4008.
12.
Hamre D, Kindig DA, Mann J. Growth and
intracellular development of a new respiratory virus. J Virol. 1967;1(4):810-6.
13.
Tyrrell DA, Bynoe ML. Cultivation of a Novel Type
of Common-Cold Virus in Organ Cultures. Br Med J. 1965;1(5448):1467-70.
14.
McIntosh K, Kapikian AZ, Turner HC, Hartley JW,
Parrott RH, Chanock RM. Seroepidemiologic studies of coronavirus infection in
adults and children. Am J Epidemiol. 1970;91(6):585-92.
15.
Cavallaro JJ, Monto AS. Community-wide outbreak of
infection with a 229E-like coronavirus in Tecumseh, Michigan. J Infect Dis.
1970;122(4):272-9.
16.
Li W, Shi Z, Yu M, Ren W, Smith C, Epstein JH, et
al. Bats are natural reservoirs of SARS-like coronaviruses. Science.
2005;310(5748):676-9.
17.
van der Hoek L, Pyrc K, Jebbink MF, Vermeulen-Oost
W, Berkhout RJ, Wolthers KC, et al. Identification of a new human coronavirus.
Nat Med. 2004;10(4):368-73.
18.
Arden KE, Nissen MD, Sloots TP, Mackay IM. New
human coronavirus, HCoV-NL63, associated with severe lower respiratory tract
disease in Australia. J Med Virol. 2005;75(3):455-62.
19.
Woo PC, Lau SK, Chu CM, Chan KH, Tsoi HW, Huang Y,
et al. Characterization and complete genome sequence of a novel coronavirus,
coronavirus HKU1, from patients with pneumonia. J Virol. 2005;79(2):884-95.
20.
de Groot RJ, Baker SC, Baric RS, Brown CS, Drosten
C, Enjuanes L, et al. Middle East respiratory syndrome corona-virus (MERS-CoV):
announcement of the Coronavirus Study Group. J Virol. 2013;87(14):7790-2.
21.
Desforges M, Le Coupanec A, Stodola JK,
Meessen-Pinard M, Talbot PJ. Human coronaviruses: viral and cellular factors
involved in neuroinvasiveness and neuropathogenesis. Virus Res. 2014;194:145-58.
22.
Yeager CL, Ashmun RA, Williams RK, Cardellichio
CB, Shapiro LH, Look AT, et al. Human aminopeptidase N is a receptor for human
coronavirus 229E. Nature. 1992;357 (6377):420-2.
23.
Cui T, Theuns S, Xie J, Van den Broeck W, Nauwynck
HJ. Role of Porcine Aminopeptidase N and Sialic Acids in Porcine Coronavirus
Infections in Primary Porcine Enterocytes. Viruses. 2020;12(4).
24.
Parks JM, Smith JC. How to discover antiviral drugs
quickly. New Eng J Med. 2020;382(23):2261-4.
25.
da Silva SJR, Alves da Silva CT, Mendes RPG, Pena
L. Role of nonstructural proteins in the pathogenesis of SARS-CoV-2. J Med
Virol. 2020;92(9):1427-9.
26.
Uddin M, Mustafa F, Rizvi TA, Loney T, Suwaidi HA,
Al-Marzouqi AHH, et al. SARS-CoV-2/COVID-19: Viral Genomics, Epidemiology,
Vaccines, and Therapeutic Interventions. Viruses. 2020;12(5).
27.
Kim D, Lee JY, Yang JS, Kim JW, Kim VN, Chang H.
The Architecture of SARS-CoV-2 Transcriptome. Cell. 2020; 181(4):914-21.e10.
28.
Robson F, Khan KS, Le TK, Paris C, Demirbag S,
Barfuss P, et al. Coronavirus RNA Proofreading: Molecular Basis and Therapeutic
Targeting. Molecular Cell. 2020;79(5):710-27.
29.
Snijder EJ, Decroly E, Ziebuhr J. The
Nonstructural Proteins Directing Coronavirus RNA Synthesis and Processing. Adv
Virus Res. 2016;96:59-126.
30.
Shin D, Mukherjee R, Grewe D, Bojkova D, Baek K,
Bhattacharya A, et al. Papain-like protease regulates SARS-CoV-2 viral spread
and innate immunity. Nature. 2020;587(7835):657-62.
31.
Jin Y, Yang H, Ji W, Wu W, Chen S, Zhang W, et al.
Virology, Epidemiology, Pathogenesis, and Control of COVID-19. Viruses.
2020;12(4).
32.
Lei X, Dong X, Ma R, Wang W, Xiao X, Tian Z, et
al. Activation and evasion of type I interferon responses by SARS-CoV-2. Nat
Commun. 2020;11(1):3810.
33.
Thoms M, Buschauer R, Ameismeier M, Koepke L, Denk
T, Hirschenberger M, et al. Structural basis for translational shutdown and
immune evasion by the Nsp1 protein of SARS-CoV-2. Science.
2020;369(6508):1249-55.
34.
Angeletti S, Benvenuto D, Bianchi M, Giovanetti M,
Pascarella S, Ciccozzi M. COVID-2019: The role of the nsp2 and nsp3 in its
pathogenesis. J Med Virol. 2020;92(6):584-8.
35.
Baez-Santos YM, St John SE, Mesecar AD. The
SARS-coronavirus papain-like protease: structure, function and inhibition by
designed antiviral compounds. Antiviral Res. 2015;115:21-38.
36.
Frieman M, Yount B, Agnihothram S, Page C,
Donaldson E, Roberts A, et al. Molecular determinants of severe acute
respiratory syndrome coronavirus pathogenesis and virulence in young and aged
mouse models of human disease. J Virol. 2012;86(2):884-97.
37.
Littler DR, Gully BS, Colson RN, Rossjohn J.
Crystal Structure of the SARS-CoV-2 Non-structural Protein 9, Nsp9. iScience.
2020;23(7):101258.
38.
Tai W, He L, Zhang X, Pu J, Voronin D, Jiang S, et
al. Characterization of the receptor-binding domain (RBD) of 2019 novel
coronavirus: implication for development of RBD protein as a viral attachment
inhibitor and vaccine. Cell Mol Immunol. 2020;17(6):613-20.
39.
Regla-Nava JA, Nieto-Torres JL, Jimenez-Guardeño
JM, Fernandez-Delgado R, Fett C, Castaño-Rodríguez C, et al. Severe acute
respiratory syndrome coronaviruses with mutations in the E protein are
attenuated and promising vaccine candidates. J Virol. 2015;89(7):3870-87.
40.
DeDiego ML, Nieto-Torres JL, Jiménez-Guardeño JM,
Regla-Nava JA, Alvarez E, Oliveros JC, et al. Severe acute respiratory syndrome
coronavirus envelope protein regulates cell stress response and apoptosis. PLoS
Pathog. 2011;7(10): e1002315.
41.
Jimenez-Guardeño JM, Nieto-Torres JL, DeDiego ML,
Regla-Nava JA, Fernandez-Delgado R, Castaño-Rodriguez C, et al. The PDZ-binding
motif of severe acute respiratory syndrome coronavirus envelope protein is a
determinant of viral pathogenesis. PLoS Pathog. 2014;10(8):e1004320.
42.
Burbelo PD, Riedo FX, Morishima C, Rawlings S, Smith
D, Das S, et al. Detection of Nucleocapsid Antibody to SARS-CoV-2 is More
Sensitive than Antibody to Spike Protein in COVID-19 Patients. medRxiv.
2020;doi:
https://doi.org/10.1101/2020.04.20.20071423.
43.
Li JY, Liao CH, Wang Q, Tan YJ, Luo R, Qiu Y, et
al. The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I
interferon signaling pathway. Virus Res. 2020;286:198074.
44.
Srinivasan S, Cui H, Gao Z, Liu M, Lu S,
Mkandawire W, et al. Structural Genomics of SARS-CoV-2 Indicates Evolutionary
Conserved Functional Regions of Viral Proteins. Viruses. 2020;12(4).
45.
Diaz J. SARS-CoV-2 Molecular Network Structure.
Front Physiol. 2020;11:870.
46.
Michel CJ, Mayer C, Poch O, Thompson JD.
Characterization of accessory genes in coronavirus genomes. Virol J.
2020;17(1):131.
47.
Castano-Rodriguez C, Honrubia JM,
Gutierrez-Alvarez J, DeDiego ML, Nieto-Torres JL, Jimenez-Guardeno JM, et al.
Role of Severe Acute Respiratory Syndrome Coronavirus Viroporins E, 3a, and 8a
in Replication and Pathogenesis. mBio. 2018;9(3).
48.
Siu KL, Yuen KS, Castaño-Rodriguez C, Ye ZW, Yeung
ML, Fung SY, et al. Severe acute respiratory syndrome corona-virus ORF3a
protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitina-tion
of ASC. Faseb j. 2019;33(8):8865-77.
49.
Issa E, Merhi G, Panossian B, Salloum T, Tokajian
S. SARS-CoV-2 and ORF3a: Nonsynonymous Mutations, Functional Domains, and Viral
Pathogenesis. mSystems. 2020;5(3).
50.
Holland LA, Kaelin EA, Maqsood R, Estifanos B, Wu
LI, Varsani A, et al. An 81-Nucleotide Deletion in SARS-CoV-2 ORF7a Identified
from Sentinel Surveillance in Arizona (January to March 2020). J Virol.
2020;94(14).
51.
Kopecky-Bromberg SA, Martinez-Sobrido L, Palese P.
7a protein of severe acute respiratory syndrome coronavirus inhibits cellular
protein synthesis and activates p38 mitogen-activated protein kinase. J Virol.
2006;80(2):785-93.
52.
Báez-Santos YM, St John SE, Mesecar AD. The
SARS-coronavirus papain-like protease: structure, function and inhibition by
designed antiviral compounds. Antiviral Res. 2015;115:21-38.
53.
Zhao J, Sun J, He W, Ji X, Gao Q, Zhai X, et al.
Snapshot of the evolution and mutation patterns of SARS-CoV-2. bioRxiv.
2020;doi:10.1101/2020.07.04.187435:2020.07.04.187435.
54.
Jauregui AR, Savalia D, Lowry VK, Farrell CM,
Wathelet MG. Identification of residues of SARS-CoV nsp1 that differentially
affect inhibition of gene expression and antiviral signaling. PloS one.
2013;8(4):e62416.
55.
Benedetti F, Snyder GA, Giovanetti M, Angeletti S,
Gallo RC, Ciccozzi M, et al. Emerging of a SARS-CoV-2 viral strain with a
deletion in nsp1. J Transl Med. 2020;18(1):329.
56.
Benvenuto D, Angeletti S, Giovanetti M, Bianchi M,
Pascarella S, Cauda R, et al. Evolutionary analysis of SARS-CoV-2: how mutation
of Non-Structural Protein 6 (NSP6) could affect viral autophagy. J Infect.
2020;81(1):e24-e7.
57.
Cornillez-Ty CT, Liao L, Yates JR, 3rd, Kuhn P,
Buchmeier MJ. Severe acute respiratory syndrome coronavirus nonstructural
protein 2 interacts with a host protein complex involved in mitochondrial
biogenesis and intracellular signaling. J Virol. 2009;83(19):10314-8.
58.
Davies JP, Almasy KM, McDonald EF, Plate L.
Comparative multiplexed interactomics of SARS-CoV-2 and homologous coronavirus
non-structural proteins identifies unique and shared host-cell dependencies.
bioRxiv. 2020;doi: https://doi.org/10.1101/2020.07.13.201517.
59.
Stobart CC, Sexton NR, Munjal H, Lu X, Molland KL,
Tomar S, et al. Chimeric exchange of coronavirus nsp5 proteases (3CLpro)
identifies common and divergent regulatory determinants of protease activity. J
Virol. 2013;87(23):12611-8.
60.
Angelini MM, Akhlaghpour M, Neuman BW, Buchmeier
MJ. Severe acute respiratory syndrome coronavirus nonstructural proteins 3, 4,
and 6 induce double-membrane vesicles. mBio. 2013;4(4).
61.
Cottam EM, Whelband MC, Wileman T. Coronavirus
NSP6 restricts autophagosome expansion. Autophagy. 2014;10 (8):1426-41.
62.
Kirchdoerfer RN, Ward AB. Structure of the
SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors. Nat Commun.
2019;10(1):2342.
63.
Rogstam A, Nyblom M, Christensen S, Sele C,
Talibov VO, Lindvall T, et al. Crystal Structure of Non-Structural Protein 10
from Severe Acute Respiratory Syndrome Coronavirus-2. Int J Mol Sci.
2020;21(19).
64.
Hillen HS, Kokic G, Farnung L, Dienemann C,
Tegunov D, Cramer P. Structure of replicating SARS-CoV-2 polymerase. Nature.
2020.
65.
Jiang Y, Yin W, Xu HE. RNA-dependent RNA
polymerase: Structure, mechanism, and drug discovery for COVID-19. Biochem
Biophys Res Commun. 2020.
66.
Gao Y, Yan L, Huang Y, Liu F, Zhao Y, Cao L, et
al. Structure of the RNA-dependent RNA polymerase from COVID-19 virus. Science.
2020;368(6492):779-82.
67.
Jang KJ, Jeong S, Kang DY, Sp N, Yang YM, Kim DE.
A high ATP concentration enhances the cooperative translocation of the SARS
coronavirus helicase nsP13 in the unwinding of duplex RNA. Sci Rep.
2020;10(1):4481.
68.
Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K,
White KM, et al. A SARS-CoV-2 protein interaction map reveals targets for drug
repurposing. Nature. 2020;583(7816):459-68.
69.
Deng X, Hackbart M, Mettelman RC, O'Brien A,
Mielech AM, Yi G, et al. Coronavirus nonstructural protein 15 mediates evasion
of dsRNA sensors and limits apoptosis in macrophages. Proc Natl Acad Sci U S A.
2017;114(21):E4251-E60.
70.
Lin S, Chen H, Ye F, Chen Z, Yang F, Zheng Y, et
al. Crystal structure of SARS-CoV-2 nsp10/nsp16 2'-O-methylase and its
implication on antiviral drug design. Signal Transduct Target Ther.
2020;5(1):131.
71.
Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N,
Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2
and Is Blocked by a Clinically Proven Protease Inhibitor. Cell.
2020;181(2):271-80 e8.
72.
Siu KL, Yuen KS, Castano-Rodriguez C, Ye ZW, Yeung
ML, Fung SY, et al. Severe acute respiratory syndrome coronavirus ORF3a protein
activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of
ASC. FASEB J. 2019;33(8):8865-77.
73.
73. Ren
Y, Shu T, Wu D, Mu J, Wang C, Huang M, et al. The ORF3a protein of SARS-CoV-2
induces apoptosis in cells. Cellular & molecular immunology.
2020;17(8):881-3.
74.
Konno Y, Kimura I, Uriu K, Fukushi M, Irie T,
Koyanagi Y, et al. SARS-CoV-2 ORF3b Is a Potent Interferon Antagonist Whose
Activity Is Increased by a Naturally Occurring Elongation Variant. Cell Rep.
2020;32(12):108185.
75.
Schoeman D, Fielding BC. Coronavirus envelope
protein: current knowledge. Virol J. 2019;16(1):69.
76.
Thomas S. The Structure of the Membrane Protein of
SARS-CoV-2 Resembles the Sugar Transporter SemiSWEET. Pathog Immun.
2020;5(1):342-63.
77.
Taylor JK, Coleman CM, Postel S, Sisk JM, Bernbaum
JG, Venkataraman T, et al. Severe Acute Respiratory Syndrome Coronavirus ORF7a
Inhibits Bone Marrow Stromal Antigen 2 Virion Tethering through a Novel
Mechanism of Glycosylation Interference. J Virol. 2015;89(23):11820-33.
78.
Pfefferle S, Krähling V, Ditt V, Grywna K,
Mühlberger E, Drosten C. Reverse genetic characterization of the natural
genomic deletion in SARS-Coronavirus strain Frankfurt-1 open reading frame 7b
reveals an attenuating function of the 7b protein in-vitro and in-vivo. Virol
J. 2009;6:131.
79.
Sung SC, Chao CY, Jeng KS, Yang JY, Lai MM. The
8ab protein of SARS-CoV is a luminal ER membrane-associated protein and induces
the activation of ATF6. Virology. 2009; 387(2): 402-13.
80.
Mu J, Xu J, Zhang L, Shu T, Wu D, Huang M, et al.
SARS-CoV-2-encoded nucleocapsid protein acts as a viral suppressor of RNA
interference in cells. Sci China Life Sci. 2020;63(9):1-4.
81.
Shi CS, Qi HY, Boularan C, Huang NN, Abu-Asab M,
Shelhamer JH, et al. SARS-coronavirus open reading frame-9b supp-resses innate
immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome. J
Immunol. 2014; 193(6):3080-9.
82.
Dominguez Andres A, Feng Y, Campos AR, Yin J, Yang
CC, James B, et al. SARS-CoV-2 ORF9c Is a Membrane-Associated Protein that
Suppresses Antiviral Responses in Cells. bioRxiv. 2020;doi:
83.
https://doi.org/10.1101/2020.08.18.256776.
84.
Thunders M, Delahunt B. Gene of the month: TMPRSS2
(transmembrane serine protease 2). J Clin Pathol. 2020; 73(12):773-6.
85.
Walls A, Park Y, Tortorici M, Wall A, McGuire A,
Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike
glycoprotein. Cell. 2020;181(2):281-92.
86.
Pillay TS. Gene of the month: the
2019-nCoV/SARS-CoV-2 novel coronavirus spike protein. J Clin Pathol. 2020;
73(7): 366-9.
87.
Bestle D, Heindl MR, Limburg H, Van Lam van T,
Pilgram O, Moulton H, et al. TMPRSS2 and furin are both essential for
proteolytic activation of SARS-CoV-2 in human airway cells. Life Sci Alliance.
2020;3(9):e202000786.
88.
Nao N, Yamagishi J, Miyamoto H, Igarashi M,
Manzoor R, Ohnuma A, et al. Genetic Predisposition To Acquire a Polybasic
Cleavage Site for Highly Pathogenic Avian Influenza Virus Hemagglutinin. mBio.
2017;8(1):e02298-16.
89.
Andersen KG, Rambaut A, Lipkin WI, Holmes EC,
Garry RF. The proximal origin of SARS-CoV-2. Nat Med. 2020;26(4):450-2.
90.
Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh
CL, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion
conformation. Science. 2020;367 (6483): 1260-3.
91.
Lu J, Sun PD. High affinity binding of SARS-CoV-2
spike protein enhances ACE2 carboxypeptidase activity. bioRxiv. 2020;doi: https://doi.org/10.1101/2020.07.01.182659.
92.
Joshi S, Joshi M, Degani M. Tackling SARS-CoV-2:
proposed targets and repurposed drugs. Future Medicinal
Chemistry.12(17):1579-601.
93.
White MA, Lin W, Cheng X. Discovery of COVID-19
Inhibitors Targeting the SARS-CoV-2 Nsp13 Helicase. J Phys Chem Lett.
2020;11(21):9144-51.
94.
Wong HH, Kumar P, Tay FP, Moreau D, Liu DX, Bard
F. Genome-Wide Screen Reveals Valosin-Containing Protein Requirement for
Coronavirus Exit from Endosomes. J Virol. 2015;89(21):11116-28.
95.
Soh WT, Liu Y, Nakayama EE, Ono C, Torii S,
Nakagami H, et al. The N-terminal domain of spike glycoprotein mediates
SARS-CoV-2 infection by associating with L-SIGN and DC-SIGN. bioRxiv.2020;doi:https://doi.org/10.1101/2020.11.05.369264:2020.11.05.369264.
96.
Huang IC, Bosch BJ, Li F, Li W, Lee KH, Ghiran S,
et al. SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L
to infect ACE2-expressing cells. J Biol Chem. 2006;281(6):3198-203.
97.
Wang K, Chen W, Zhou Y-S, Lian J-Q, Zhang Z, Du P,
et al. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein.
bioRxiv. 2020; doi:
https://doi.org/10.1101/2020.03.14.988345.
98.
Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H, et
al. Structural basis of receptor recognition by SARS-CoV-2. Nature.
2020;581(7807):221-4.
99.
Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman
R, et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging
human coronavirus-EMC. Nature. 2013;495(7440):251-4.
100. Hulswit
RJG, Lang Y, Bakkers MJG, Li W, Li Z, Schouten A, et al. Human coronaviruses
OC43 and HKU1 bind to 9-O-acetylated sialic acids via a conserved
receptor-binding site in spike protein domain A. Proceedings of the National
Academy of Sciences. 2019;116(7):2681-90.
101. Coutard
B, Valle C, de Lamballerie X, Canard B, Seidah NG, Decroly E. The spike
glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage
site absent in CoV of the same clade. Antiviral Res. 2020;176:104742.
102. Ibrahim
IM, Abdelmalek DH, Elshahat ME, Elfiky AA. COVID-19 spike-host cell receptor
GRP78 binding site prediction. J Infect. 2020;80(5):554-62.
103. Zhao
X, Zheng S, Chen D, Zheng M, Li X, Li G, et al. LY6E Restricts the Entry of
Human Coronaviruses, Including the Currently Pandemic SARS-CoV-2. J Virol.
2020.
104. Milanetti
E, Miotto M, Di Rienzo L, Monti M, Gosti G, Ruocco G. In-Silico evidence for
two receptors based strategy of SARS-CoV-2. 2020;24(https://arxiv.org/abs/2003.11107).
105. Renteria
AE, Endam Mfuna L, Adam D, Filali-Mouhim A, Maniakas A, Rousseau S, et al.
Azithromycin Downregulates Gene Expression of IL-1beta and Pathways Involving
TMPRSS2 and TMPRSS11D Required by SARS-CoV-2. Am J Respir Cell Mol Biol. 2020.
106. Paulpandi
M, Kavithaa K, Asaikkutty A, Balachandar V, Ayyadurai N, Arul N. Could host
cell receptor alteration prevent SARS-CoV-2 viral entry? - Hype or hope. Eur
Rev Med Pharmacol Sci. 2020;24(8):4554-7.
107. Turner
AJ. Chapter 25 - ACE2 Cell Biology, Regulation, and Physiological Functions.
In: Unger T, Steckelings UM, dos Santos RAS, editors. The Protective Arm of the
Renin Angiotensin System (RAS). Boston: Academic Press; 2015. p. 185-9.
108. Uhlén
M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, et al.
Proteomics. Tissue-based map of the human proteome. Science.
2015;347(6220):1260419.
109. Li W,
Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angiotensin-converting
enzyme 2 is a functional receptor for the SARS coronavirus. Nature.
2003;426(6965):450-4.
110. Li F,
Li W, Farzan M, Harrison SC. Structure of SARS coronavirus spike
receptor-binding domain complexed with receptor. Science.
2005;309(5742):1864-8.
111. Wan Y,
Shang J, Graham R, Baric RS, Li F. Receptor Recognition by the Novel
Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of
SARS Coronavirus. J Virol. 2020;94(7).
112. Xu H,
Zhong L, Deng J, Peng J, Dan H, Zeng X, et al. High expression of ACE2 receptor
of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci.
2020;12(1):8.
113. Ali F,
Elserafy M, Alkordi MH, Amin M. ACE2 coding variants in different populations
and their potential impact on SARS-CoV-2 binding affinity. Biochem Biophys Rep.
2020:100798.
114. Ferrario
C, Jessup J, Chappell M, Averill D, Brosnihan K, Tallant E, et al. Effect of
Angiotensin-Converting Enzyme Inhibition and Angiotensin II Receptor Blockers
on Cardiac Angiotensin-Converting Enzyme 2. Circulation. 2005;111(20):2605-10.
115. Diaz
JH. Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin
receptor blockers may increase the risk of severe COVID-19. Journal of Travel
Medicine. 2020;27(3).
116. Hippisley-Cox
J, Young D, Coupland C, Channon KM, Tan PS, Harrison DA, et al. Risk of severe
COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort
study including 8.3 million people. Heart. 2020;106:1503-11.
117. de
Abajo FJ, Rodriguez-Martin S, Lerma V, Mejia-Abril G, Aguilar M, Garcia-Luque
A, et al. Use of renin-angiotensin-aldosterone system inhibitors and risk of
COVID-19 requiring admission to hospital: a case-population study. Lancet.
2020;395(10238):1705-14.
118. Kuba
K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. A crucial role of angiotensin
converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med.
2005;11(8):875-9.
119. Hikmet
F, Méar L, Edvinsson Å, Micke P, Uhlén M, Lindskog C. The protein expression
profile of ACE2 in human tissues. Molecular Systems Biology. 2020;16(7):e9610.
120. Chappel
MC, Ferrario CM. ACE and ACE2: their role to balance the expression of
angiotensin II and angiotensin-(1-7). Kidney Int. 2006;70(1):8-10.
121. Gaddam
RR, Chambers S, Bhatia M. ACE and ACE2 in inflammation: a tale of two enzymes.
Inflamm Allergy Drug Targets. 2014;13(4):224-34.
122. 121. Santos RAS, Oudit GY, Verano-Braga T, Canta G,
Steckelings UM, Bader M. The renin-angiotensin system: going beyond the
classical paradigms. Am J Physiol Heart Circ Physiol. 2019;316(5):H958-h70.
123. Ocaranza
MP, Godoy I, Jalil JE, Varas M, Collantes P, Pinto M, et al. Enalapril
attenuates downregulation of Angiotensin-converting enzyme 2 in the late phase
of ventricular dysfunction in myocardial infarcted rat. Hypertension.
2006;48(4):572-8.
124. Nataraj
C, Oliverio MI, Mannon RB, Mannon PJ, Audoly LP, Amuchastegui CS, et al.
Angiotensin II regulates cellular immune responses through a calcineurin-dependent
pathway. The Journal of clinical investigation. 1999;104(12):1693-701.
125. Pagliaro
P, Penna C. ACE/ACE2 Ratio: A Key Also in 2019 Coronavirus Disease (Covid-19)?
Front Med (Lausanne). 2020;7:335.
126. Qiu X,
Tian Y, Jiang X, Xu J, Zhang Q, Huang J. Clinical Characteristics of
Coronavirus Disease 19. Glob Clin Transl Res. 2020;2(3):85-99.
127. Wu Z,
Hu R, Zhang C, Ren W, Yu A, Zhou X. Elevation of plasma angiotensin II level is
a potential pathogenesis for the critically ill COVID-19 patients. Critical
Care. 2020;24(1):290.
128. Chung
MK, Karnik S, Saef J, Bergmann C, Barnard J, Lederman MM, et al. SARS-CoV-2 and
ACE2: The biology and clinical data settling the ARB and ACEI controversy.
EBioMedicine. 2020;58:102907.
129. Achua
JK, Chu KY, Ibrahim E, Khodamoradi K, Delma KS, Iakymenko OA, et al.
Histopathology and Ultrastructural Findings of Fatal COVID-19 Infections on
Testis. World J Mens Health. 2020.
130. Bradley
BT, Maioli H, Johnston R, Chaudhry I, Fink SL, Xu H, et al. Histopathology and
ultrastructural findings of fatal COVID-19 infections in Washington State: a
case series. Lancet. 2020;396(10247):320-32.
131. Sonzogni
A, Previtali G, Seghezzi M, Grazia Alessio M, Gianatti A, Licini L, et al.
Liver histopathology in severe COVID 19 respiratory failure is suggestive of
vascular alterations. Liver Int. 2020;40(9):2110-6.
132. Ackermann
M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. Pulmonary
Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N Engl J
Med. 2020;383(2):120-8.
133. Chaipan
C, Kobasa D, Bertram S, Glowacka I, Steffen I, Tsegaye TS, et al. Proteolytic
activation of the 1918 influenza virus hemagglutinin. Journal of virology.
2009;83(7):3200-11.
134. Iwata-Yoshikawa
N, Okamura T, Shimizu Y, Hasegawa H, Takeda M, Nagata N. TMPRSS2 Contributes to
Virus Spread and Immunopathology in the Airways of Murine Models after
Coronavirus Infection. J Virol. 2019;93(6).
135. Zhang
F, Hughes C. Clinical epidemiology of coronavirus disease 2019: defined on
current research. Glob Clin Transl Res. 2020;2(3):54-72.
136. Stopsack
KH, Mucci LA, Antonarakis ES, Nelson PS, Kantoff PW. TMPRSS2 and COVID-19:
Serendipity or Opportunity for Intervention? Cancer Discov. 2020;10(6):779-82.
137. Strope
JD, Pharm DC, Figg WD. TMPRSS2: Potential Biomarker for COVID-19 Outcomes. J
Clin Pharmacol. 2020;60(7):801-7.
138. Renteria
AE, Mfuna Endam L, Adam D, Filali-Mouhim A, Maniakas A, Rousseau S, et al.
Azithromycin Downregulates Gene Expression of IL-1beta and Pathways Involving
TMPRSS2 and TMPRSS11D Required by SARS-CoV-2. Am J Respir Cell Mol Biol. 2020;63(5):707-9.
139. Hoffmann
M, Kleine-Weber H, Pohlmann S. A Multibasic Cleavage Site in the Spike Protein
of SARS-CoV-2 Is Essential for Infection of Human Lung Cells. Mol Cell.
2020;78(4):779-84 e5.
140. Lukassen
S, Chua RL, Trefzer T, Kahn NC, Schneider MA, Muley T, et al. SARS-CoV-2
receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient
secretory cells. EMBO J. 2020;39(10):e105114.
141. Drak
Alsibai K. Expression of angiotensin-converting enzyme 2 and proteases in
COVID-19 patients: A potential role of cellular FURIN in the pathogenesis of
SARS-CoV-2. Med Hypotheses. 2020;143:109893.
142. Mentlein
R. Dipeptidyl-peptidase IV (CD26)--role in the inactivation of regulatory
peptides. Regul Pept. 1999;85(1):9-24.
143. Chen
X. Biochemical properties of recombinant prolyl dipeptidases DPP-IV and DPP8.
Adv Exp Med Biol. 2006;575:27-32.
144. Kolb
AF, Maile J, Heister A, Siddell SG. Characterization of functional domains in
the human coronavirus HCV 229E receptor. J Gen Virol. 1996;77 ( Pt 10):2515-21.
145. Kolb
AF, Hegyi A, Siddell SG. Identification of residues critical for the human
coronavirus 229E receptor function of human aminopeptidase N. J Gen Virol.
1997;78 ( Pt 11):2795-802.
146. Bassendine
MF, Bridge SH, McCaughan GW, Gorrell MD. Covid-19 and co-morbidities: a role
for Dipeptidyl Peptidase 4 (DPP4) in disease severity? J Diabetes. 2020.
147. Vankadari
N, Wilce JA. Emerging WuHan (COVID-19) coronavirus: glycan shield and structure
prediction of spike glycoprotein and its interaction with human CD26. Emerg
Microbes Infect. 2020;9(1):601-4.
148. Morimoto
C, Schlossman SF. The structure and function of CD26 in the T-cell immune
response. Immunological Reviews. 1998;161(1):55-70.
149. Barchetta
I, Cavallo MG, Baroni MG. COVID-19 and diabetes: Is this association driven by
the DPP4 receptor? Potential clinical and therapeutic implications. Diabetes
Res Clin Pract. 2020;163:108165.
150. Strollo
R, Pozzilli P. DPP4 inhibition: Preventing SARS-CoV-2 infection and/or
progression of COVID-19? Diabetes Metab Res Rev. 2020:e3330.
151. Wang
K, Chen W, Zhou Y-S, Lian J-Q, Zhang Z, Du P, et al. SARS-CoV-2 invades host
cells via a novel route: CD147-spike protein. bioRxiv. 2020:2020.03.14.988345.
152. Crosnier
C, Bustamante LY, Bartholdson SJ, Bei AK, Theron M, Uchikawa M, et al. Basigin
is a receptor essential for erythrocyte invasion by Plasmodium falciparum.
Nature. 2011;480(7378):534-7.
153. Ulrich
H, Pillat MM. CD147 as a Target for COVID-19 Treatment: Suggested Effects of
Azithromycin and Stem Cell Engagement. Stem Cell Rev Rep. 2020;16(3):434-40.
154. Bian
H, Zheng Z-H, Wei D, Zhang Z, Kang W-Z, Hao C-Q, et al. Meplazumab treats
COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical
trial. medRxiv. 2020;doi: https://doi.org/10.1101/2020.03.21.20040691.
155. Chen
Z, Mi L, Xu J, Yu J, Wang X, Jiang J, et al. Function of HAb18G/CD147 in
invasion of host cells by severe acute respiratory syndrome coronavirus. J
Infect Dis. 2005;191(5):755-60.
156. Rosas
IO, Richards TJ, Konishi K, Zhang Y, Gibson K, Lokshin AE, et al. MMP1 and MMP7
as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis. PLoS
Med. 2008;5(4):e93.
157. George
PM, Wells AU, Jenkins RG. Pulmonary fibrosis and COVID-19: the potential role
for antifibrotic therapy. The Lancet Respiratory Medicine. 2020;8(8):807-15.
158. Radzikowska
U, Ding M, Tan G, Zhakparov D, Peng Y, Wawrzyniak P, et al. Distribution of
ACE2, CD147, CD26, and other SARS-CoV-2 associated molecules in tissues and
immune cells in health and in asthma, COPD, obesity, hyper-tension, and
COVID-19 risk factors. Allergy. 2020;75 (11): 2829-45.
159. Ibrahim
IM, Abdelmalek DH, Elfiky AA. GRP78: A cell's response to stress. Life Sci.
2019;226:156-63.
160. Palmeira
A, Sousa E, Koseler A, Sabirli R, Goren T, Turkcuer I, et al. Preliminary
Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with
SARS-CoV-2 Infection. Pharmaceuticals (Basel). 2020;13(6):132.
161. Sudeep
HV, Gouthamchandra K, Shyamprasad K. Molecular docking analysis of Withaferin A
from Withania somnifera with the Glucose regulated protein 78 (GRP78) receptor
and the SARS-CoV-2 main protease. Bioinformation. 2020;16(5):411-7.
162. Ou X,
Liu Y, Lei X, Li P, Mi D, Ren L, et al. Characterization of spike glycoprotein
of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat
Commun. 2020;11(1):1620.
163. Daniloski
Z, Jordan TX, Wessels H-H, Hoagland DA, Kasela S, Legut M, et al.
Identification of Required Host Factors for SARS-CoV-2 Infection in Human
Cells. Cell.
164. Yu J,
Liu SL. Emerging Role of LY6E in Virus-Host Interactions. Viruses.
2019;11(11):1020;https://doi.org/10.3390/v11111020.
165. Zhao
X, Li J, Winkler CA, An P, Guo JT. IFITM Genes, Variants, and Their Roles in
the Control and Pathogenesis of Viral Infections. Front Microbiol. 2018;9:3228.
166. Chen
D, Hou Z, Jiang D, Zheng M, Li G, Zhang Y, et al. GILT restricts the cellular
entry mediated by the envelope glycoproteins of SARS-CoV, Ebola virus and Lassa
fever virus. Emerg Microbes Infect. 2019;8(1):1511-23.
167. Liu
SY, Aliyari R, Chikere K, Li G, Marsden MD, Smith JK, et al.
Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by
production of 25-hydroxycholesterol. Immunity. 2013;38(1):92-105.
168. Shu Q,
Lennemann NJ, Sarkar SN, Sadovsky Y, Coyne CB. ADAP2 Is an Interferon
Stimulated Gene That Restricts RNA Virus Entry. PLoS Pathog.
2015;11(9):e1005150.
169. Yu J,
Liu SL. Emerging Role of LY6E in Virus-Host Interactions. Viruses. 2019;11(11).
170. Ille
AM, Kishel E, Bodea R, Ille A, Lamont H, Amico-Ruvio S. Protein LY6E as a
candidate for mediating transport of adeno-associated virus across the human
blood-brain barrier. J Neurovirol. 2020;26:769–78.
171. Luo L,
McGarvey P, Madhavan S, Kumar R, Gusev Y, Upadhyay G. Distinct lymphocyte
antigens 6 (Ly6) family members Ly6D, Ly6E, Ly6K and Ly6H drive tumorigenesis
and clinical outcome. Oncotarget. 2016;7(10):11165-93.
172. Gardner
JP, Durso RJ, Arrigale RR, Donovan GP, Maddon PJ, Dragic T, et al. L-SIGN (CD
209L) is a liver-specific capture receptor for hepatitis C virus. Proceedings
of the National Academy of Sciences. 2003;100(8):4498-503.
173. Olofsson
S, Kumlin U, Dimock K, Arnberg N. Avian influenza and sialic acid receptors:
more than meets the eye? Lancet Infect Dis. 2005;5(3):184-8.
174. Li W,
Hulswit RJG, Widjaja I, Raj VS, McBride R, Peng W, et al. Identification of
sialic acid-binding function for the Middle East respiratory syndrome coronavirus
spike glycoprotein. Proc Natl Acad Sci U S A. 2017;114(40):E8508-e17.
175. Fantini
J, Di Scala C, Chahinian H, Yahi N. Structural and molecular modelling studies
reveal a new mechanism of action of chloroquine and hydroxychloroquine against
SARS-CoV-2 infection. Int J Antimicrob Agents. 2020; 55(5):105960.
176. Wielgat
P, Rogowski K, Godlewska K, Car H. Coronaviruses: Is Sialic Acid a Gate to the
Eye of Cytokine Storm? From the Entry to the Effects. Cells. 2020;9(9):1963;
https://doi.org/10.3390/cells9091963.
177. Engin
AB, Engin ED, Engin A. Dual function of sialic acid in gastrointestinal
SARS-CoV-2 infection. Environ Toxicol Pharmacol. 2020;79:103436.
178. Seth
S, Batra J, Srinivasan S. COVID-19: Targeting Proteases in Viral Invasion and
Host Immune Response. Front Mol Biosci. 2020;7:215.
179. Ji HL,
Zhao R, Matalon S, Matthay MA. Elevated Plasmin-(ogen) as a Common Risk Factor
for COVID-19 Susceptibility. Physiol Rev. 2020;100(3):1065-75.
180. Kaur
U, Chakrabarti SS, Ojha B, Pathak BK, Singh A, Saso L, et al. Targeting host
cell proteases to prevent SARS-CoV-2 invasion. Curr Drug Targets. 2020,
https://doi.org/10.2174/1389450121666200924113243.
181. Umemura
Y, Yamakawa K, Kiguchi T, Nishida T, Kawada M, Fujimi S. Hematological
Phenotype of COVID-19-Induced Coagulopathy: Far from Typical Sepsis-Induced
Coagulopathy. J Clin Med. 2020;9(9):2875; https://doi.org/10.3390/jcm9092875.
182. Huang Y,
Lyu X, Li D, Wang L, Wang Y, Zou W, et al. A cohort study of 676 patients
indicates D-dimer is a critical risk factor for the mortality of COVID-19. PLoS
One. 2020;15(11):e0242045.
183. Solun
B, Shoenfeld Y. Inhibition of metalloproteinases in therapy for severe lung
injury due to COVID-19. Med Drug Discov. 2020;7:100052.
184. Thierry
AR. Anti-protease Treatments Targeting Plasmin(ogen) and Neutrophil Elastase
May Be Beneficial in Fighting COVID-19. Physiol Rev. 2020;100(4):1597-8.
185. Heissig
B, Salama Y, Takahashi S, Osada T, Hattori K. The multifaceted role of
plasminogen in inflammation. Cell Signal. 2020;75:109761.