Article Review: Toll-like Receptors and COVID-19

Authors

  • May K. Ismael Department of Biology, College of Science, University of Baghdad, Baghdad, IRAQ.

DOI:

https://doi.org/10.31033/ijrasb.9.2.11

Keywords:

Corona virus, Respiratory syndrome, SARS‐CoV‐2, TLRs

Abstract

By March 2020, a pandemic had been emerged Corona Virus Infection in 2019 (COVID-19), which was triggered through the sensitive pulmonary syndrome (SARS disease corona virus- 2 (SARS COV-2). Overall precise path physiology of SARS COV-2 still unknown, as does the involvement of every element of the acute or adaptable immunity systems. Additionally, evidence from additional corona virus groups, including SARS COV as well as the Middle East pulmonary disease, besides that, fresh discoveries might help researchers fully comprehend SARS CoV-2. Toll-like receptors (TLRs) serve a critical part in both detection of viral particles as well as the stimulation of the body's immune response. When TLR systems are activated, pro-inflammatory cytokines like interleukin 1 (IL1), IL6, or nuclear factors, in addition to helpful interferon, are secreted. TLRs such as TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, or TLR9 might possibly have a role in COVID-19 infections. It's also important noting that while dealing with COVID-19 infections, researchers should consider both the good or detrimental impacts of TLR. TLRs might be a focus for reducing infections inside the initial phases of the illness or developing a SARS CoV-2 vaccine.

Downloads

Download data is not yet available.

References

Karki R., Sharma B.R., Tuladhar S., Williams E.P., Zalduondo L., Samir P., Zheng M., Sundaram B., Banoth B., Malireddi R.K.S., et al. Synergism of TNF-alpha and IFN-gamma Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes. Cell. 2021;184:149–168. doi: 10.1016/j.cell.2020.11.025.

Al-Tawfiq J.A., Petersen E., Memish Z.A., Perlman S., Zumla A. Middle East respiratory syndrome coronavirus—The need for global proactive surveillance, sequencing and modeling. Travel Med. Infect. Dis. 2021;43:102118. doi: 10.1016/j.tmaid.2021.102118.

Mesel-Lemoine M., Millet J., Vidalain P.O., Law H., Vabret A., Lorin V., Escriou N., Albert M.L., Nal B., Tangy F. A human coronavirus responsible for the common cold massively kills dendritic cells but not monocytes. J. Virol. 2012;86:7577–7587. doi: 10.1128/JVI.00269-12.

Wu A., Peng Y., Huang B., Ding X., Wang X., Niu P., Meng J., Zhu Z., Zhang Z., Wang J., et al. Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China. Cell Host Microbe. 2020;27:325–328. doi: 10.1016/j.chom.2020.02.001.

Lu R., Zhao X., Li J., Niu P., Yang B., Wu H., Wang W., Song H., Huang B., Zhu N., et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet. 2020;395:565–574. doi: 10.1016/S0140-6736(20)30251-8.

Ren L.L., Wang Y.M., Wu Z.Q., Xiang Z.C., Guo L., Xu T., Jiang Y.Z., Xiong Y., Li Y.J., Li X.W., et al. Identification of a novel coronavirus causing severe pneumonia in human: A descriptive study. Chin. Med. J. 2020;133:1015–1024. doi: 10.1097/CM9.0000000000000722.

Chan J.F., Kok K.H., Zhu Z., Chu H., To K.K., Yuan S., Yuen K.Y. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg. Microbes Infect. 2020;9:221–236. doi: 10.1080/22221751.2020.1719902.

Cubuk J., Alston J.J., Incicco J.J., Singh S., Stuchell-Brereton M.D., Ward M.D., Zimmerman M.I., Vithani N., Griffith D., Wagoner J.A., et al. The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA. Nat. Commun. 2021;12:1936. doi: 10.1038/s41467-021-21953-3.

Kang S., Yang M., Hong Z., Zhang L., Huang Z., Chen X., He S., Zhou Z., Zhou Z., Chen Q., et al. Crystal structure of SARS-CoV-2 nucleocapsid protein RNA binding domain reveals potential unique drug targeting sites. Acta Pharm. Sin. B. 2020;10:1228–1238. doi: 10.1016/j.apsb.2020.04.009.

Walls A.C., Park Y.J., Tortorici M.A., Wall A., McGuire A.T., Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell. 2020;181:281–292. doi: 10.1016/j.cell.2020.02.058.

Shang J., Wan Y., Luo C., Ye G., Geng Q., Auerbach A., Li F. Cell entry mechanisms of SARS-CoV-2. Proc. Natl. Acad. Sci. USA. 2020;117:11727–11734. doi: 10.1073/pnas.2003138117.

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;78:779–784. doi: 10.1016/j.molcel.2020.04.022.

Ou X., Liu Y., Lei X., Li P., Mi D., Ren L., Guo L., Guo R., Chen T., Hu J., et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat. Commun. 2020;11:1620. doi: 10.1038/s41467-020-15562-9.

Hoffmann M., Kleine-Weber H., Schroeder S., Kruger N., Herrler T., Erichsen S., Schiergens T.S., Herrler G., Wu N.H., Nitsche A., et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181:271–280. doi: 10.1016/j.cell.2020.02.052.

Zhao M.M., Yang W.L., Yang F.Y., Zhang L., Huang W.J., Hou W., Fan C.F., Jin R.H., Feng Y.M., Wang Y.C., et al. Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development. Signal Transduct. Target. Ther. 2021;6:134. doi: 10.1038/s41392-021-00558-8.

Padmanabhan P., Desikan R., Dixit N.M. Targeting TMPRSS2 and Cathepsin B/L together may be synergistic against SARS-CoV-2 infection. PLoS Comput. Biol. 2020;16:e1008461. doi: 10.1371/journal.pcbi.1008461.

Klein S., Cortese M., Winter S.L., Wachsmuth-Melm M., Neufeldt C.J., Cerikan B., Stanifer M.L., Boulant S., Bartenschlager R., Chlanda P. SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography. Nat. Commun. 2020;11:5885. doi: 10.1038/s41467-020-19619-7.

Harrison A.G., Lin T., Wang P. Mechanisms of SARS-CoV-2 Transmission and Pathogenesis. Trends Immunol. 2020;41:1100–1115. doi: 10.1016/j.it.2020.10.004.

Finkel Y., Mizrahi O., Nachshon A., Weingarten-Gabbay S., Morgenstern D., Yahalom-Ronen Y., Tamir H., Achdout H., Stein D., Israeli O., et al. The coding capacity of SARS-CoV-2. Nature. 2021;589:125–130. doi: 10.1038/s41586-020-2739-1.

Hillen H.S., Kokic G., Farnung L., Dienemann C., Tegunov D., Cramer P. Structure of replicating SARS-CoV-2 polymerase. Nature. 2020;584:154–156. doi: 10.1038/s41586-020-2368-8.

Mendonca L., Howe A., Gilchrist J.B., Sheng Y., Sun D., Knight M.L., Zanetti-Domingues L.C., Bateman B., Krebs A.S., Chen L., et al. Correlative multi-scale cryo-imaging unveils SARS-CoV-2 assembly and egress. Nat. Commun. 2021;12:4629. doi: 10.1038/s41467-021-24887-y.

Horova V., Landova B., Hodek J., Chalupsky K., Krafcikova P., Chalupska D., Duchoslav V., Weber J., Boura E., Klima M. Localization of SARS-CoV-2 Capping Enzymes Revealed by an Antibody against the nsp10 Subunit. Viruses. 2021;13:1487. doi: 10.3390/v13081487.

Ghosh S., Dellibovi-Ragheb T.A., Kerviel A., Pak E., Qiu Q., Fisher M., Takvorian P.M., Bleck C., Hsu V.W., Fehr A.R., et al. β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway. Cell. 2020;183:1520–1535. doi: 10.1016/j.cell.2020.10.039.

Li D., Wu M. Pattern recognition receptors in health and diseases. Signal Transduct. Target. Ther. 2021;6:291. doi: 10.1038/s41392-021-00687-0.

Ziegler C.G.K., Allon S.J., Nyquist S.K., Mbano I.M., Miao V.N., Tzouanas C.N., Cao Y., Yousif A.S., Bals J., Hauser B.M., et al. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell. 2020;181:1016–1035. doi: 10.1016/j.cell.2020.04.035.

Zou X., Chen K., Zou J., Han P., Hao J., Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front. Med. 2020;14:185–192. doi: 10.1007/s11684-020-0754-0.

Qi F., Qian S., Zhang S., Zhang Z. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem. Biophys. Res. Commun. 2020;526:135–140. doi: 10.1016/j.bbrc.2020.03.044.

Zheng M., Karki R., Williams E.P., Yang D., Fitzpatrick E., Vogel P., Jonsson C.B., Kanneganti T.D. TLR2 senses the SARS-CoV-2 envelope protein to produce inflammatory cytokines. Nat. Immunol. 2021;22:829–838. doi: 10.1038/s41590-021-00937-x.

Bortolotti D., Gentili V., Rizzo S., Schiuma G., Beltrami S., Strazzabosco G., Fernandez M., Caccuri F., Caruso A., Rizzo R.J.M. TLR3 and TLR7 RNA Sensor Activation during SARS-COV-2 Infection. Microorganisms. 2021;9:1820. doi: 10.3390/microorganisms9091820.

Bezemer G.F.G., Garssen J. TLR9 and COVID-19: A Multidisciplinary Theory of a Multifaceted Therapeutic Target. Front. Pharm. 2020;11:601685. doi: 10.3389/fphar.2020.601685.

Zhao Y., Kuang M., Li J., Zhu L., Jia Z., Guo X., Hu Y., Kong J., Yin H., Wang X., et al. SARS-CoV-2 spike protein interacts with and activates TLR41. Cell Res. 2021;31:818–820. doi: 10.1038/s41422-021-00495-9.

Shirato K., Kizaki T. SARS-CoV-2 spike protein S1 subunit induces pro-inflammatory responses via toll-like receptor 4 signaling in murine and human macrophages. Heliyon. 2021;7:e06187. doi: 10.1016/j.heliyon.2021.e06187.

Salvi V., Nguyen H.O., Sozio F., Schioppa T., Gaudenzi C., Laffranchi M., Scapini P., Passari M., Barbazza I., Tiberio L., et al. SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8. JCI Insight. 2021;6:150542. doi: 10.1172/jci.insight.150542.

Takeuchi O., Sato S., Horiuchi T., Hoshino K., Takeda K., Dong Z., Modlin R.L., Akira S. Cutting edge: Role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J. Immunol. 2002;169:10–14. doi: 10.4049/jimmunol.169.1.10.

Takeuchi O., Hoshino K., Kawai T., Sanjo H., Takada H., Ogawa T., Takeda K., Akira S. Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity. 1999;11:443–451. doi: 10.1016/S1074-7613(00)80119-3.

Kang J.Y., Nan X., Jin M.S., Youn S.J., Ryu Y.H., Mah S., Han S.H., Lee H., Paik S.G., Lee J.O. Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer. Immunity. 2009;31:873–884. doi: 10.1016/j.immuni.2009.09.018.

Alexopoulou L., Holt A.C., Medzhitov R., Flavell R.A. Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature. 2001;413:732–738. doi: 10.1038/35099560.

Poltorak A., He X., Smirnova I., Liu M.Y., Van Huffel C., Du X., Birdwell D., Alejos E., Silva M., Galanos C., et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: Mutations in Tlr4 gene. Science. 1998;282:2085–2088. doi: 10.1126/science.282.5396.2085.

Georgel P., Jiang Z., Kunz S., Janssen E., Mols J., Hoebe K., Bahram S., Oldstone M.B., Beutler B. Vesicular stomatitis virus glycoprotein G activates a specific antiviral Toll-like receptor 4-dependent pathway. Virology. 2007;362:304–313. doi: 10.1016/j.virol.2006.12.032.

Haynes L.M., Moore D.D., Kurt-Jones E.A., Finberg R.W., Anderson L.J., Tripp R.A. Involvement of toll-like receptor 4 in innate immunity to respiratory syncytial virus. J. Virol. 2001;75:10730–10737. doi: 10.1128/JVI.75.22.10730-10737.2001.

Kurt-Jones E.A., Popova L., Kwinn L., Haynes L.M., Jones L.P., Tripp R.A., Walsh E.E., Freeman M.W., Golenbock D.T., Anderson L.J., et al. Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat. Immunol. 2000;1:398–401. doi: 10.1038/80833.

Hayashi F., Smith K.D., Ozinsky A., Hawn T.R., Yi E.C., Goodlett D.R., Eng J.K., Akira S., Underhill D.M., Aderem A. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature. 2001;410:1099–1103. doi: 10.1038/35074106.

Gewirtz A.T., Navas T.A., Lyons S., Godowski P.J., Madara J.L. Cutting edge: Bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. J. Immunol. 2001;167:1882–1885. doi: 10.4049/jimmunol.167.4.1882.

Lund J.M., Alexopoulou L., Sato A., Karow M., Adams N.C., Gale N.W., Iwasaki A., Flavell R.A. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc. Natl. Acad. Sci. USA. 2004;101:5598–5603. doi: 10.1073/pnas.0400937101.

Diebold S.S., Kaisho T., Hemmi H., Akira S., Reis e Sousa C. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science. 2004;303:1529–1531. doi: 10.1126/science.1093616.

Heil F., Hemmi H., Hochrein H., Ampenberger F., Kirschning C., Akira S., Lipford G., Wagner H., Bauer S. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science. 2004;303:1526–1529. doi: 10.1126/science.1093620.

Hemmi H., Takeuchi O., Kawai T., Kaisho T., Sato S., Sanjo H., Matsumoto M., Hoshino K., Wagner H., Takeda K., et al. A Toll-like receptor recognizes bacterial DNA. Nature. 2000;408:740–745. doi: 10.1038/35047123.

Zhang Q., Raoof M., Chen Y., Sumi Y., Sursal T., Junger W., Brohi K., Itagaki K., Hauser C.J. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464:104–107. doi: 10.1038/nature08780.

Hasan U., Chaffois C., Gaillard C., Saulnier V., Merck E., Tancredi S., Guiet C., Briere F., Vlach J., Lebecque S., et al. Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88. J. Immunol. 2005;174:2942–2950. doi: 10.4049/jimmunol.174.5.2942.

Hess N.J., Jiang S., Li X., Guan Y., Tapping R.I. TLR10 Is a B Cell Intrinsic Suppressor of Adaptive Immune Responses. J. Immunol. 2017;198:699–707. doi: 10.4049/jimmunol.1601335.

Fore F., Indriputri C., Mamutse J., Nugraha J. TLR10 and Its Unique Anti-Inflammatory Properties and Potential Use as a Target in Therapeutics. Immune Netw. 2020;20:e21. doi: 10.4110/in.2020.20.e21.

Marks K.E., Cho K., Stickling C., Reynolds J.M. Toll-like Receptor 2 in Autoimmune Inflammation. Immune Netw. 2021;21:e18. doi: 10.4110/in.2021.21.e18.

Kawasaki T., Kawai T. Toll-like receptor signaling pathways. Front. Immunol. 2014;5:461. doi: 10.3389/fimmu.2014.00461.

Oliveira-Nascimento L., Massari P., Wetzler L.M. The Role of TLR2 in Infection and Immunity. Front. Immunol. 2012;3:79. doi: 10.3389/fimmu.2012.00079.

Sariol A., Perlman S. SARS-CoV-2 takes its Toll. Nat. Immunol. 2021;22:801–802. doi: 10.1038/s41590-021-00962-w.

Khan S., Shafiei M.S., Longoria C., Schoggins J., Savani R.C., Zaki H. SARS-CoV-2 spike protein induces inflammation via TLR2-dependent activation of the NF-kappaB pathway. bioRxiv. 2021 doi: 10.1101/2021.03.16.435700.

Choudhury A., Mukherjee S. In silico studies on the comparative characterization of the interactions of SARS-CoV-2 spike glycoprotein with ACE-2 receptor homologs and human TLRs. J. Med. Virol. 2020;92:2105–2113. doi: 10.1002/jmv.25987.

Sohn K.M., Lee S.G., Kim H.J., Cheon S., Jeong H., Lee J., Kim I.S., Silwal P., Kim Y.J., Paik S., et al. COVID-19 Patients Upregulate Toll-like Receptor 4-mediated Inflammatory Signaling That Mimics Bacterial Sepsis. J. Korean Med. Sci. 2020;35:e343. doi: 10.3346/jkms.2020.35.e343.

Li Y., Renner D.M., Comar C.E., Whelan J.N., Reyes H.M., Cardenas-Diaz F.L., Truitt R., Tan L.H., Dong B., Alysandratos K.D., et al. SARS-CoV-2 induces double-stranded RNA-mediated innate immune responses in respiratory epithelial-derived cells and cardiomyocytes. Proc. Natl. Acad. Sci. USA. 2021;118:e2022643118. doi: 10.1073/pnas.2022643118.

Li Y., Chen M., Cao H., Zhu Y., Zheng J., Zhou H. Extraordinary GU-rich single-strand RNA identified from SARS coronavirus contributes an excessive innate immune response. Microbes Infect. 2013;15:88–95. doi: 10.1016/j.micinf.2012.10.008.

Digard P., Lee H.M., Sharp C., Grey F., Gaunt E. Intra-genome variability in the dinucleotide composition of SARS-CoV-2. Virus Evol. 2020;6:veaa057. doi: 10.1093/ve/veaa057.

Blasius A.L., Beutler B. Intracellular toll-like receptors. Immunity. 2010;32:305–315. doi: 10.1016/j.immuni.2010.03.012.

Mielcarska M.B., Bossowska-Nowicka M., Toka F.N. Cell Surface Expression of Endosomal Toll-Like Receptors-A Necessity or a Superfluous Duplication? Front. Immunol. 2020;11:620972. doi: 10.3389/fimmu.2020.620972.

Ioannidis I., Ye F., McNally B., Willette M., Flano E. Toll-like receptor expression and induction of type I and type III interferons in primary airway epithelial cells. J. Virol. 2013;87:3261–3270. doi: 10.1128/JVI.01956-12.

Kanno A., Tanimura N., Ishizaki M., Ohko K., Motoi Y., Onji M., Fukui R., Shimozato T., Yamamoto K., Shibata T., et al. Targeting cell surface TLR7 for therapeutic intervention in autoimmune diseases. Nat. Commun. 2015;6:6119. doi: 10.1038/ncomms7119.

Onji M., Kanno A., Saitoh S., Fukui R., Motoi Y., Shibata T., Matsumoto F., Lamichhane A., Sato S., Kiyono H., et al. An essential role for the N-terminal fragment of Toll-like receptor 9 in DNA sensing. Nat. Commun. 2013;4:1949. doi: 10.1038/ncomms2949.

Matsumoto M., Kikkawa S., Kohase M., Miyake K., Seya T. Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling. Biochem. Biophys. Res. Commun. 2002;293:1364–1369. doi: 10.1016/S0006-291X(02)00380-7.

Murakami Y., Fukui R., Motoi Y., Kanno A., Shibata T., Tanimura N., Saitoh S., Miyake K. Roles of the cleaved N-terminal TLR3 fragment and cell surface TLR3 in double-stranded RNA sensing. J. Immunol. 2014;193:5208–5217. doi: 10.4049/jimmunol.1400386.

Murakami Y., Fukui R., Motoi Y., Shibata T., Saitoh S.I., Sato R., Miyake K. The protective effect of the anti-Toll-like receptor 9 antibody against acute cytokine storm caused by immunostimulatory DNA. Sci. Rep. 2017;7:44042. doi: 10.1038/srep44042.

Lindau D., Mussard J., Wagner B.J., Ribon M., Ronnefarth V.M., Quettier M., Jelcic I., Boissier M.C., Rammensee H.G., Decker P. Primary blood neutrophils express a functional cell surface Toll-like receptor 9. Eur. J. Immunol. 2013;43:2101–2113. doi: 10.1002/eji.201142143.

Guan W.J., Ni Z.Y., Hu Y., Liang W.H., Ou C.Q., He J.X., Liu L., Shan H., Lei C.L., Hui D.S.C., et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N. Engl. J. Med. 2020;382:1708–1720. doi: 10.1056/NEJMoa2002032.

Russell C.D., Millar J.E., Baillie J.K. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020;395:473–475. doi: 10.1016/S0140-6736(20)30317-2.

Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., Qiu Y., Wang J., Liu Y., Wei Y., et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet. 2020;395:507–513. doi: 10.1016/S0140-6736(20)30211-7.

Schijns V., Lavelle E.C. Prevention and treatment of COVID-19 disease by controlled modulation of innate immunity. Eur J. Immunol. 2020;50:932–938. doi: 10.1002/eji.202048693.

Mukherjee R., Bhattacharya A., Bojkova D., Mehdipour A.R., Shin D., Khan K.S., Hei-Yin Cheung H., Wong K.B., Ng W.L., Cinatl J., et al. Famotidine inhibits toll-like receptor 3-mediated inflammatory signaling in SARS-CoV-2 infection. J. Biol. Chem. 2021;297:100925. doi: 10.1016/j.jbc.2021.100925.

Mekonnen D., Mengist H.M. and Jin T. SARS-CoV-2 subunit vaccine adjuvants and their signaling pathways. Expert Review of Vaccines. 2022;21(1):69–81.doi: 10.1080/14760584.2021.1991794.

Downloads

Published

2022-03-21

How to Cite

May K. Ismael. (2022). Article Review: Toll-like Receptors and COVID-19. International Journal for Research in Applied Sciences and Biotechnology, 9(2), 78–95. https://doi.org/10.31033/ijrasb.9.2.11

Issue

Section

Articles