A review on SARS-CoV2 drug regimens inferring plausible mechanisms to impede the viral propagation and cytokine storm

Poulomi Chatterjee, Niladri Prasad Mishra, Abhishek Das, Sagar Acharya


A sharp outbreak of pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) in early 2020, has shaken up the whole global health care system and economy with its rapid chain-of-infection and high mortality index. This article emphasizes on the immunopathology of virus and current drug therapies. We have put down a compendious postulation on different drug actions vis-à-vis their reversing strategies for the pertinent diseases. A critical analysis has been made on the cytokine storm and focusing on to the interplays among lymphocytes and other innate immune cells (NK cells, macrophages, dendritic cells etc.) with secreted cytokines as well as on to the drug effectiveness by tallying with the contexts of SARS-CoV and Middle East respiratory syndrome coronavirus infections. The hustle and bustle is ongoing for repurposing existing drugs, designed for other infectious microbes. Tackling the adversities in anti-viral treatment has become too challenging to stop this contagion. Thereafter, the scientific front liners are on trials of hundreds of drugs by making comparisons to other contagious epidemics. Current review summarizes different drug actions on viral propagation and host immunomodulation. Our conjecture will intrigue to re-evaluate the mostly used drugs at present state.


SARS-CoV2, Cytokine storm, Anti-viral drugs, Remdesivir, Favipiravir, Immunopathology

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Zaki AM, Van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. New Eng J Med. 2012;367(19):1814-20.

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet. 2020; 395(10223):497-506.

Su S, Wong G, Shi W, Liu J, Lai AC, Zhou J, et al. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol. 2016;24(6):490-502.

Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. New Eng J Med. 2020;382(18):1708-20.

Wong CK, Lam CW, Wu AK, Ip WK, Lee NL, Chan IH, et al. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol. 2004;136(1):95-103.

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):1-5.

Addi AB, Lefort A, Hua X, Libert F, Communi D, Ledent C, et al. Modulation of murine dendritic cell function by adenine nucleotides and adenosine: involvement of the A2B receptor. Eur J Immunol. 2008;38(6):1610-20.

Ma DY, Suthar MS. Mechanisms of innate immune evasion in re-emerging RNA viruses. Current Opinion Virol. 2015;12:26-37.

Mazaleuskaya L, Veltrop R, Ikpeze N, Martin-Garcia J, Navas-Martin S. Protective role of Toll-like receptor 3-induced type I interferon in murine coronavirus infection of macrophages. Viruses. 2012; 4(5):901-23.

Chow KT, Gale JM, Loo YM. RIG-I and other RNA sensors in antiviral immunity. Ann Rev Immunol. 2018;36:667-94.

Kindler E, Thiel V, Weber F. Interaction of SARS and MERS coronaviruses with the antiviral interferon response. In: Advances in virus research. USA: Academic Press; 2016:96;219-43.

Ahmadpoor P, Rostaing L. Why the immune system fails to mount an adaptive immune response to a Covid‐19 infection. Transplant Int. 2020;85:53-9.

Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clin Immunol. 2020; 25:108393.

Croker BA, O’Donnell JA, Gerlic M. Pyroptotic death storms and cytopenia. Curr Opinion Immunol. 2014;26:128-37.

Agostini ML, Andres EL, Sims AC, Graham RL, Sheahan TP, Lu X, et al. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio. 2018;9(2).

Jordan PC, Liu C, Raynaud P, Lo MK, Spiropoulou CF, Symons JA, et al. Initiation, extension, and termination of RNA synthesis by a paramyxovirus polymerase. PLoS. 2018;14(2):e1006889.

Gordon CJ, Tchesnokov EP, Feng JY, Porter DP, Götte M. The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus. J Biol Chem. 2020;295(15):4773-9.

Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral research. 2013; 100(2):446-54.

Sangawa H, Komeno T, Nishikawa H, Yoshida A, Takahashi K, Nomura N, et al. Mechanism of action of T-705 ribosyl triphosphate against influenza virus RNA polymerase. Antimicrobial agents and chemotherapy. 2013;57(11):5202-8.

Khalili JS, Zhu H, Mak NS, Yan Y, Zhu Y. Novel coronavirus treatment with ribavirin: Groundwork for an evaluation concerning COVID‐19. Journal of medical virology. 2020;55:98-105.

Zhuang MW, Cheng Y, Zhang J, Jiang XM, Wang L, Deng J, et al. Increasing host cellular receptor—angiotensin‐converting enzyme 2 (ace2) expression by coronavirus may facilitate 2019‐nCoV (or SARS‐CoV‐2) Infection. J Med Virol. 2020;80:59-67.

Ballabio A, Bonifacino JS. Lysosomes as dynamic regulators of cell and organismal homeostasis. Nature Rev Mol Cell Biol. 2019;2:1-8.

Schrezenmeier E, Dörner T. Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nature Rev Rheumatol. 2020;16 (3):155-66.

Rokni M, Ghasemi V, Tavakoli Z. Immune responses and pathogenesis of SARS‐CoV‐2 during an outbreak in Iran: Comparison with SARS and MERS. Rev Med Virol. 2020;30(3):e2107.

Meyerowitz EA, Vannier AG, Friesen MG, Schoenfeld S, Gelfand JA, Callahan MV, et al. Rethinking the role of hydroxychloroquine in the treatment of COVID‐19. The FASEB J. 2020;34(5): 6027-37.

Lokugamage KG, Hage A, Schindewolf C, Rajsbaum R, Menachery VD. SARS-CoV-2 is sensitive to type I interferon pretreatment. BioRxiv. 2020;97:58-68.

Hoffman HM, Broderick L. JAK inhibitors in autoinflammation. J Clin Invest. 2018;128(7):2760-62.

Stebbing J, Phelan A, Griffin I, Tucker C, Oechsle O, Smith D, et al. COVID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect Dis. 2020;20(4):400-2.

Virtanen AT, Haikarainen T, Raivola J, Silvennoinen O. Selective JAKinibs: prospects in inflammatory and autoimmune diseases. BioDrugs. 2019;33(1):15-32.

Misra DP, Agarwal V, Gasparyan AY, Zimba O. Rheumatologists’ perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets. Clin Rheumatol. 2020;39(7):2055-2.

He G, Massarella J, Ward P. Clinical pharmacokinetics of the prodrug oseltamivir and its active metabolite Ro 64-0802. Clin Pharm. 1999; 37(6):471-84.

Zhang XW, Yap YL. The 3D structure analysis of SARS-CoV S1 protein reveals a link to influenza virus neuraminidase and implications for drug and antibody discovery. J Mol Stru. 2004;681(1-3):137-1.

Rossignol JF, La Frazia S, Chiappa L, Ciucci A, Santoro MG. Thiazolides, a new class of anti-influenza molecules targeting viral hemagglutinin at the post-translational level. J Biol Chem. 2009;284 (43):29798-808.

Nicolas P, Maia MF, Bassat Q, Kobylinski KC, Monteiro W, Rabinovich NR, et al. Safety of oral ivermectin during pregnancy: a systematic review and meta-analysis. Lancet Global Health. 2020;8(1):e92-100.

Wagstaff KM, Rawlinson SM, Hearps AC, Jans DA. An AlphaScreen®-based assay for high-throughput screening for specific inhibitors of nuclear import. J Biomol Screen. 2011;16(2):192-200.

Wagstaff KM, Sivakumaran H, Heaton SM, Harrich D, Jans DA. Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochem J. 2012;443(3):851-6.

Wulan WN, Heydet D, Walker EJ, Gahan ME, Ghildyal R. Nucleocytoplasmic transport of nucleocapsid proteins of enveloped RNA viruses. Front Microbiol. 2015;6:553.

Wang Q, Zhao Y, Chen X, An H. Virtual screening of approved clinic drugs with main protease (3CL pro) reveals potential inhibitory effects on SARS-CoV-2. J Biol Chem. 2020;52:67-9.

Sham HL, Kempf DJ, Molla A, Marsh KC, Kumar GN, Chen CM, et al. ABT-378, a highly potent inhibitor of the human immunodeficiency virus protease. Antimicrob Agents Chemother. 1998;42 (12):3218-24.

Murphy RL, Brun S, Hicks C, Eron JJ, Gulick R, King M, et al. ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviral-naive adults with HIV-1 infection: 48-week results. Aids. 2001;15(1):F1-9.

Cvetkovic RS, Goa KL. Lopinavir/ritonavir: A review of its use in the management of HIV infection. Drugs. 2003;63(8):769-2.

Nukoolkarn V, Lee VS, Malaisree M, Aruksakulwong O, Hannongbua S. Molecular dynamic simulations analysis of ritronavir and lopinavir as SARS-CoV 3CLpro inhibitors. J Theor Biol. 2008;254(4):861-7.

Anand K, Ziebuhr J, Wadhwani P, Mesters JR, Hilgenfeld R. Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs. Science. 2003;300(5626):1763-7.

Soo YO, Cheng Y, Wong R, Hui DS, Lee CK, Tsang KK, et al. Retrospective comparison of convalescent plasma with continuing high‐dose methylprednisolone treatment in SARS patients. Clinical microbiology and infection. 2004;10(7):676-8.

Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, et al. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA. 2020;323(16):1582-9.

Kumar GV, Jeyanthi V, Ramakrishnan S. A short review on antibody therapy for COVID-19. New Microbes New Infect. 2020:100682.

Casadevall A, Pirofski LA. The convalescent sera option for containing COVID-19. The Journal of clinical investigation. 2020;130(4):1545-8.

Hoffmann M, Kleine-Weber H, Schroeder S, Krüger 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;45:87-95.

Tian X, Li C, Huang A, Xia S, Lu S, Shi Z, et al. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg Microbes Infec. 2020;9(1):382-5.

Wang C, Li W, Drabek D, Okba NM, van Haperen R, Osterhaus AD, van Kuppeveld FJ, et al. A human monoclonal antibody blocking SARS-CoV-2 infection. Nature Commu. 2020;11(1):1-6.