Treatment Strategies for COVID 19: New Insights from Comparative Genome Analysis, Pathophysiology, Host-Virus Interaction and Immune Response

Athira M Menon, Tushar Ivanti, Ankita Sharma, Sunil Dutta Purohit, Joginder Singh Saklani, Abhishek Kumar, Narendra Kumar Sharma, Amit Sharma, Tikam Chand Dakal

Abstract


The recent outbreak of Coronavirus (SARS-CoV-2, earlier known as 2019-nCoV) in Wuhan City, China and its subsequent spread in other countries have posed a big threat to human health. The speed with which this virus has spread across the globe was unimaginably fast that within a span of 2 months, more than 100 countries became victims of its vicious trap. As of today, there is no potent therapeutic regime available in any form (drug, vaccine or other) for effective treatment of COVID19. In this review, we have presented therapeutic solution of COVID 19 based of understanding drawn from comparative genome analysis, pathophysiology, host-virus interaction and immune response. Herein, we have presented the genomic and structural organization of the virus have been studied which pose an immense resemblance with the previously reported coronaviruses. The SARS-CoV-2 is highly contagious and its infectivity is unimaginably high as compared to all previously known coronaviruses such as SARS-CoV-1, MERS-CoV, CoV-NL63, CoV-229E, CoV-HUK1, CoV-OC43 and others. Further, we aimed to describe the complex etiology, deregulated immune response and other pathophysiological outcomes of SARS-CoV-2 infection so as to define their unimaginable high infectivity and transmission properties. In addition, we discuss about the current status of screening tests, drugs, reprofiled drugs, vaccines and other therapies that are under different stages of development. The biorhythm and host response on infection have also been studied which can sanguinely open the door for treatment of the disease. No vaccination or drug candidate has been identified yet but the use of the repurposed drug of its ancestors and other related causal organisms have shown promising results and recovery of the patients.


Keywords


Coronavirus, Genome Structure, Life cycle of SARS-CoV-2, Spike Protein, Therapeutics

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References


Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, Hu Y, Tao ZW, Tian JH, Pei YY, Yuan ML. A new coronavirus associated with human respiratory disease in China. Nature. 2020 Mar;579(7798):265-9.

WHO draft landscape of COVID 19 Candidate vaccine list. (2020) https://www.who.int/blueprint/priority-diseases/key-action/Novel_Coronavirus_Landscape_nCoV_11April2020.PDF?ua=1

Dakal TC. SARS-CoV-2 attachment to host cells is possibly mediated via RGD-integrin interaction in a calcium-dependent manner. OSF Preprints. (2020a).

Dakal TC. Antigenic sites in SARS-CoV-2 spike RBD show molecular similarity with antigens from fifteen pathogenic microorganisms and harbor peptides for vaccine development. Frontiers in Immunology. (2020b). Submitted.

Li K, Fang Y, Li W, Pan C, Qin P, Zhong Y, Liu X, Huang M, Liao Y, Li S. CT image visual quantitative evaluation and clinical classification of coronavirus disease (COVID-19). European radiology. 2020 Mar 25:1-0.

Weiss SR, Navas-Martin S. Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiology and molecular biology reviews. 2005 Dec 1;69(4):635-64.

Beniac DR, Andonov A, Grudeski E, Booth TF. Architecture of the SARS coronavirus prefusion spike. Nature structural & molecular biology. 2006 Aug;13(8):751-2.

Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The lancet. 2020 Feb 15;395(10223):497-506.

Jiang S, Shi Z, Shu Y, Song J, Gao GF, Tan W, Guo D. A distinct name is needed for the new coronavirus. Lancet (London, England). 2020 Mar 21;395(10228):949.

Alexander DJ, Gough RE. Isolation of avian infectious bronchitis virus from experimentally infected chickens. Research in Veterinary Science. 1977 Nov 1;23(3):344-7.

Ng LF, Hiscox JA. Coronaviruses in animals and humans.

Zhou P, Lou YX, Wang XG, Hu B, Zhang L, Zhang W. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature [Internet]. 2020; 579 (7798): 270–3.

Beury D, Fléchon L, Maurier F, Caboche S, Varré JS, Touzet H, Faure K, Dubuisson J, Hot D, Guéry B, Goffard A. Use of whole-genome sequencing in the molecular investigation of care-associated HCoV-OC43 infections in a hematopoietic stem cell transplant unit. Journal of Clinical Virology. 2020 Jan 1; 122:104206.

Kahn JS, McIntosh K. History and recent advances in coronavirus discovery. The Pediatric infectious disease journal. 2005 Nov 1;24(11):S223-7.

Zhou Z, Sun Y, Yan X, Tang X, Li Q, Tan Y, Lan T, Ma J. Swine acute diarrhea syndrome coronavirus (SADS-CoV) antagonizes interferon-β production via blocking IPS-1 and RIG-I. Virus research. 2020 Mar 1;278:197843.

Goumenou M, Spandidos DA, Tsatsakis A. Possibility of transmission through dogs being a contributing factor to the extreme Covid 19 outbreak in North Italy. Molecular Medicine Reports. 2020 Jun 1;21(6):2293-5.

Tai W, He L, Zhang X, Pu J, Voronin D, Jiang S, Zhou Y, Du L. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cellular & molecular immunology. 2020 Jun;17(6):613-20.

Wang W, Tang J, Wei F. Updated understanding of the outbreak of 2019 novel coronavirus (2019‐nCoV) in Wuhan, China. Journal of medical virology. 2020 Apr;92(4):441-7.

Wassenaar TM, Zou Y. 2019_nCoV/SARS‐CoV‐2: rapid classification of betacoronaviruses and identification of Traditional Chinese Medicine as potential origin of zoonotic coronaviruses. Letters in Applied Microbiology. 2020 May;70(5):342-8.

Sohrabi C, Alsafi Z, O’Neill N, Khan M, Kerwan A, Al-Jabir A, Iosifidis C, Agha R. World Health Organization declares global emergency: A review of the 2019 novel coronavirus (COVID-19). International Journal of Surgery. 2020 Feb 26.

Daga MK, Kumar N, Aarthi J, Mawari G, Garg S, Rohatgi I. From SARS-CoV to Coronavirus Disease 2019 (COVID-19)-A Brief Review. Journal of Advanced Research in Medicine (E-ISSN: 2349-7181 & P-ISSN: 2394-7047). 2019;6(4):1-9.

Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. Journal of medical virology. 2020 Apr;92(4):418-23.

Zhu N, Zhang D, Wang W. China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China, 2019 [published January 24, 2020]. N Engl J Med

Sawicki SG, Sawicki DL, Younker D, Meyer Y, Thiel V, Stokes H, Siddell SG. Functional and genetic analysis of coronavirus replicase-transcriptase proteins. PLoS Pathogens. 2005 Dec 9;1(4):e39.

Weiss SR, Leibowitz JL. Coronavirus pathogenesis. InAdvances in virus research 2011 Jan 1 (Vol. 81, pp. 85-164). Academic Press.

Wu A, Peng Y, Huang B, Ding X, Wang X, Niu P, Meng J, Zhu Z, Zhang Z, Wang J, Sheng J. Genome composition and divergence of the novel coronavirus (2019-nCoV) originating in China. Cell host & microbe. 2020 Feb 7.

Ruch TR, Machamer CE. The coronavirus E protein: assembly and beyond. Viruses. 2012 Mar;4(3):363-82.

Pervushin K, Tan E, Parthasarathy K, Lin X, Jiang FL, Yu D, Vararattanavech A, Soong TW, Liu DX, Torres J. Structure and inhibition of the SARS coronavirus envelope protein ion channel. PLoS Pathog. 2009 Jul 10;5(7):e1000511.

Westerbeck JW, Machamer CE. The infectious bronchitis coronavirus envelope protein alters Golgi pH to protect the spike protein and promote the release of infectious virus. Journal of virology. 2019 Jun 1;93(11).

Risco C, Antón IM, Suñé C, Pedregosa AM, Martin-Alonso JM, Parra F, Carrascosa JL, Enjuanes L. Membrane protein molecules of transmissible gastroenteritis coronavirus also expose the carboxy-terminal region on the external surface of the virion. Journal of virology. 1995 Sep 1;69(9):5269-77.

Perrier A, Bonnin A, Desmarets L, Danneels A, Goffard A, Rouillé Y, Dubuisson J, Belouzard S. The C-terminal domain of the MERS coronavirus M protein contains a trans-Golgi network localization signal. Journal of Biological Chemistry. 2019 Sep 27;294(39):14406-21.

Cong Y, Ulasli M, Schepers H, Mauthe M, V’kovski P, Kriegenburg F, Thiel V, de Haan CA, Reggiori F. Nucleocapsid protein recruitment to replication-transcription complexes plays a crucial role in coronaviral life cycle. Journal of virology. 2020 Jan 31;94(4).

Lin Z, Gao Q, Qian F, Jinlian M, Lishi Z, Tian C, Yu Q, Zhenhua C, Ping W, Lin B. The nucleocapsid protein of SARS-CoV-2 abolished pluripotency in human induced pluripotent stem cells. Available at SSRN 3561932. 2020 Mar 26.

Cavanagh D. Coronavirus avian infectious bronchitis virus. Veterinary research. 2007 Mar 1;38(2):281-97

SALLENAVE JM, Guillot L. Host signaling and proteolytic pathways in the resolution or the exacerbation of coronavirus (CoV-2) infection in COVID-19 disease: what therapeutic targets?.

Zhong NS, Zheng BJ, Li YM, Poon LL, Xie ZH, Chan KH, Li PH, Tan SY, Chang Q, Xie JP, Liu XQ. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003. The Lancet. 2003 Oct 25;362(9393):1353-8.

Nicholls JM, Butany J, Poon LL, Chan KH, Beh SL, Poutanen S, Peiris JM, Wong M. Time course and cellular localization of SARS-CoV nucleoprotein and RNA in lungs from fatal cases of SARS. PLoS Med. 2006 Jan 3;3(2):e27.

Pyrc K, Berkhout B, Van Der Hoek L. The novel human coronaviruses NL63 and HKU1. Journal of virology. 2007 Apr 1;81(7):3051-7.

Alraddadi BM, Watson JT, Almarashi A, Abedi GR, Turkistani A, Sadran M, Housa A, Almazroa MA, Alraihan N, Banjar A, Albalawi E. Risk factors for primary Middle East respiratory syndrome coronavirus illness in humans, Saudi Arabia, 2014. Emerging infectious diseases. 2016 Jan;22(1):49.

Oboho IK, Tomczyk SM, Al-Asmari AM, Banjar AA, Al-Mugti H, Aloraini MS, Alkhaldi KZ, Almohammadi EL, Alraddadi BM, Gerber SI, Swerdlow DL. 2014 MERS-CoV outbreak in Jeddah—a link to health care facilities. New England Journal of Medicine. 2015 Feb 26;372(9):846-54.

Du L, Kou Z, Ma C, Tao X, Wang L, Zhao G, Chen Y, Yu F, Tseng CT, Zhou Y, Jiang S. A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines. PloS one. 2013 Dec 4;8(12):e81587.

Guo YR, Cao QD, Hong ZS, Tan YY, Chen SD, Jin HJ, Tan KS, Wang DY, Yan Y. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak–an update on the status. Military Medical Research. 2020 Dec;7(1):1-0.

Sahu KK, Mishra AK, Lal A. Comprehensive update on current outbreak of novel coronavirus infection (2019-nCoV). Annals of Translational Medicine. 2020 Mar;8(6).

Grifoni A, Sidney J, Zhang Y, Scheuermann RH, Peters B, Sette A. March 2020, posting date. A sequence homology and bioinformatic approach can predict candidate targets for immune responses to SARS-CoV-2. Cell Host Microbe https://doi. org/10.1016/j. chom. 2020;2.

Xu J, Zhao S, Teng T, Abdalla AE, Zhu W, Xie L, Wang Y, Guo X. Systematic comparison of two animal-to-human transmitted human coronaviruses: SARS-CoV-2 and SARS-CoV. Viruses. 2020 Feb;12(2):244.

Abdullahi IN, Emeribe AU, Mustapha JO, Fasogbon SA, Ofor IB, Opeyemi IS, Obi-George C, Sunday AO, Nwofe J. Exploring the genetics, ecology of SARS-COV-2 and climatic factors as possible control strategies against COVID-19. Infez Med. 2020;28(2):166-73..

Shafique L, Ihsan A, Liu Q. Evolutionary trajectory for the emergence of novel coronavirus SARS-CoV-2. Pathogens. 2020 Mar;9(3):240.

Ahmed SF, Quadeer AA, McKay MR. Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies. Viruses. 2020 Mar;12(3):254.

Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, Yuen KY. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerging microbes & infections. 2020 Jan 1;9(1):221-36.

Othman H, Bouslama Z, Brandenburg JT, Da Rocha J, Hamdi Y, Ghedira K, Srairi-Abid N, Hazelhurst S. Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism. Biochemical and Biophysical Research Communications. 2020 May 14.

Lv L, Li G, Chen J, Liang X, Li Y. Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13. BioRxiv. 2020 Jan 1..

Gu H, Chu DK, Peiris M, Poon LL. Multivariate analyses of codon usage of SARS-CoV-2 and other betacoronaviruses. Virus Evolution. 2020 Jan;6(1):veaa032..

Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol 2020; 5: 562-9.

Belouzard S, Chu VC, Whittaker GR. Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proceedings of the National Academy of Sciences. 2009 Apr 7;106(14):5871-6.

Shereen MA, Khan S, Kazmi A, Bashir N, Siddique R. COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses. Journal of Advanced Research. 2020 Mar 16.

Matsuyama S, Ujike M, Morikawa S, Tashiro M, Taguchi F. Protease-mediated enhancement of severe acute respiratory syndrome coronavirus infection. Proceedings of the National Academy of Sciences. 2005 Aug 30;102(35):12543-7.

Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Müller MA. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020 Mar 5.

Monteil V, Kwon H, Prado P, Hagelkrüys A, Wimmer RA, Stahl M, Leopoldi A, Garreta E, Del Pozo CH, Prosper F, Romero JP. Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell. 2020 Apr 24.

Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, Guo L, Guo R, Chen T, Hu J, Xiang Z. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nature communications. 2020 Mar 27;11(1):1-2.

Tang X, Wu C, Li X, Song Y, Yao X, Wu X, Duan Y, Zhang H, Wang Y, Qian Z, Cui J. On the origin and continuing evolution of SARS-CoV-2. National Science Review. 2020 Mar.

De Wit E, Van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nature Reviews Microbiology. 2016 Aug;14(8):523.

Masters PS. The molecular biology of coronaviruses. Advances in virus research. 2006 Jan 1;66:193-292.

Song Z, Xu Y, Bao L, Zhang L, Yu P, Qu Y, Zhu H, Zhao W, Han Y, Qin C. From SARS to MERS, thrusting coronaviruses into the spotlight. Viruses. 2019 Jan;11(1):59.

Gu J, Korteweg C. Pathology and pathogenesis of severe acute respiratory syndrome. The American journal of pathology. 2007 Apr 1;170(4):1136-47.

Docea AO, Tsatsakis A, Albulescu D, Cristea O, Zlatian O, Vinceti M, Moschos SA, Tsoukalas D, Goumenou M, Drakoulis N, Dumanov JM. A new threat from an old enemy: Re emergence of coronavirus. International journal of molecular medicine. 2020 Jun 1;45(6):1631-43.

Ferretti L, Wymant C, Kendall M, Zhao L, Nurtay A, Bonsall DG, Fraser C. Quantifying dynamics of SARS-CoV-2 transmission suggests that epidemic control and avoidance is feasible through instantaneous digital contact tracing. medRxiv. 2020 Jan 1.

Zhao J, Zhao J, Mangalam AK, Channappanavar R, Fett C, Meyerholz DK, Agnihothram S, Baric RS, David CS, Perlman S. Airway memory CD4+ T cells mediate protective immunity against emerging respiratory coronaviruses. Immunity. 2016 Jun 21;44(6):1379-91.

Zhou G, Zhao Q. Perspectives on therapeutic neutralizing antibodies against the Novel Coronavirus SARS-CoV-2. International Journal of Biological Sciences. 2020;16(10):1718.

Lei S, Jiang F, Su W. Clinical characteristics andoutcomes of patients undergoing surgeries during the incubationperiod of COVID-19 infection. EClinicalMedicine. 2020: 100331.

Rothan HA, Byrareddy SN. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. Journal of autoimmunity. 2020 Feb 26:102433.

Engin AB, Engin ED, Engin A. Two important controversial risk factors in SARS-CoV-2 infection: obesity and smoking. Environmental Toxicology and Pharmacology. 2020 May 15:103411.

Shi Y, Wang Y, Shao C, Huang J, Gan J, Huang X, Bucci E, Piacentini M, Ippolito G, Melino G. COVID-19 infection: the perspectives on immune responses.

Ferrari C, Barili V, Varchetta S, Mondelli MU. Immune mechanisms of viral clearance and disease pathogenesis during viral hepatitis. The liver: biology and pathobiology. 2020 Feb 12:821-50.

Tseng CT, Perrone LA, Zhu H, Makino S, Peters CJ. Severe acute respiratory syndrome and the innate immune responses: modulation of effector cell function without productive infection. The Journal of Immunology. 2005 Jun 15;174(12):7977-85.

Szollosi DE, Mathias CB, Lucero V, Ahmad S, Donato J. Immunopathogenesis, Immunization, and Treatment of Infectious Diseases. InPharmacology of Immunotherapeutic Drugs 2020 (pp. 277-319). Springer, Cham.

Jain N, Shankar U, Majee P, Kumar A. Scrutinizing the SARS-CoV-2 protein information for the designing an effective vaccine encompassing both the T-cell and B-cell epitopes. BioRxiv. 2020 Jan 1.

Peng H, Yang LT, Wang LY, Li J, Huang J, Lu ZQ, Koup RA, Bailer RT, Wu CY. Long-lived memory T lymphocyte responses against SARS coronavirus nucleocapsid protein in SARS-recovered patients. Virology. 2006 Aug 1;351(2):466-75.

Li L, Huang Q, Wang DC, Ingbar DH, Wang X. Acute lung injury in patients with COVID‐19 infection. Clinical and Translational Medicine. 2020 Jan;10(1):20-7.

Law PK. Emergent serum therapy and antibody medicine to counteract sudden attacks of COVID-19 and other pathogenic epidemics.

Berger A. Th1 and Th2 responses: what are they?. Bmj. 2000 Aug 12;321(7258):424.

Kaiko GE, Horvat JC, Beagley KW, Hansbro PM. Immunological decision‐making: how does the immune system decide to mount a helper T‐cell response?. Immunology. 2008 Mar;123(3):326-38.

Hoffman W, Lakkis FG, Chalasani G. B cells, antibodies, and more. Clinical Journal of the American Society of Nephrology. 2016 Jan 7;11(1):137-54.

Janeway CA, Travers P, Walport M, Capra JD. Immunobiology: the immune system in health and disease. 1997. The recognition of antigen.:79-194.

Mäkelä S. Activation of Innate Immune Responses by Toll-Like Receptors and Influenza Viruses.

Almolda B, Gonzalez B, Castellano B. Antigen presentation in EAE: role of microglia, macrophages and dendritic cells. Front Biosci. 2011 Jan 1;16(1):1157-71.

Caligiuri MA. Human natural killer cells. Blood, The Journal of the American Society of Hematology. 2008 Aug 1;112(3):461-9.

Strapazzon G, Hilty MP, Bouzat P, Pratali L, Brugger H, Rauch S. To compare the incomparable: COVID-19 pneumonia and high altitude disease. European Respiratory Journal. 2020 Jan 1.

Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, Camporota L. COVID-19 pneumonia: different respiratory treatments for different phenotypes?.

Wu J, Zha P. Preventive, Mitigating and Treatment Strategies for Containing or Ending The COVID-19 Pandemic.

Al-helfawi MA. Potential Approach for Fighting Against Corona Virus Disease. American Scientific Research Journal for Engineering, Technology, and Sciences (ASRJETS). 2020 Mar 22;66(1):127-44.

Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. The cytokine release syndrome (CRS) of severe COVID-19 and interleukin-6 receptor (IL-6R) antagonist tocilizumab may be the key to reduce the mortality. International journal of antimicrobial agents. 2020 Mar 29.

Ye Q, Wang B, Mao J. Cytokine storm in COVID-19 and treatment. Journal of Infection. 2020 Apr 10.

Leiva-Juárez MM, Kolls JK, Evans SE. Lung epithelial cells: therapeutically inducible effectors of antimicrobial defense. Mucosal immunology. 2018 Jan;11(1):21-34.

Herold S, Steinmueller M, von Wulffen W, Cakarova L, Pinto R, Pleschka S, Mack M, Kuziel WA, Corazza N, Brunner T, Seeger W. Lung epithelial apoptosis in influenza virus pneumonia: the role of macrophage-expressed TNF-related apoptosis-inducing ligand. The Journal of experimental medicine. 2008 Dec 22;205(13):3065-77.

Högner K, Wolff T, Pleschka S, Plog S, Gruber AD, Kalinke U, Walmrath HD, Bodner J, Gattenlöhner S, Lewe-Schlosser P, Matrosovich M. Macrophage-expressed IFN-β contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia. PLoS Pathog. 2013 Feb 28;9(2):e1003188.

Liu Q, Wang RS, Qu GQ, Wang YY, Liu P, Zhu YZ, Fei G, Ren L, Zhou YW, Liu L. Gross examination report of a COVID-19 death autopsy. Fa yi xue za zhi. 2020 Feb 25;36(1):21.

Wan S, Yi Q, Fan S, Lv J, Zhang X, Guo L, Lang C, Xiao Q, Xiao K, Yi Z, Qiang M. Relationships among lymphocyte subsets, cytokines, and the pulmonary inflammation index in coronavirus (COVID‐19) infected patients. British journal of haematology. 2020 May;189(3):428-37.

Amemiya K, Dankmeyer JL, Bearss JJ, Zeng X, Stonier SW, Soffler C, Cote CK, Welkos SL, Fetterer DP, Chance TB, Trevino SR. Dysregulation of TNF-α and IFN-γ expression is a common host immune response in a chronically infected mouse model of melioidosis when comparing multiple human strains of Burkholderia pseudomallei. BMC immunology. 2020 Dec 1;21(1):5.

Korber B, Fischer W, Gnanakaran SG, Yoon H, Theiler J, Abfalterer W, Foley B, Giorgi EE, Bhattacharya T, Parker MD, Partridge DG. Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2. bioRxiv. 2020 Jan 1.

Xie L, Sun C, Luo C, Zhang Y, Zhang J, Yang J, Chen L, Yang J, Li J. SARS-CoV-2 and SARS-CoV spike-RBD structure and receptor binding comparison and potential implications on neutralizing antibody and vaccine development. bioRxiv. 2020 Jan 1.

Rosa SG, Santos WC. Clinical trials on drug repositioning for COVID-19 treatment. Revista Panamericana de Salud Pública. 2020 May 8;44:e40.

Zhu S, Guo X, Geary K, Zhang D. Emerging Therapeutic Strategies for COVID-19 patients. Discoveries. 2020 Jan;8(1).

Chakraborty S. Why re-purposing HIV drugs Lopinavir/ritonavir to inhibit the SARS-Cov2 protease probably wont work-but re-purposing Ribavirin might since it has a very similar binding site within the RNA-polymerase.

Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020 Mar 4;105932(10.1016).

Li Y, Xie Z, Lin W, Cai W, Wen C, Guan Y, Mo X, Wang J, Wang Y, Peng P, Chen X. An exploratory randomized, controlled study on the efficacy and safety of lopinavir/ritonavir or arbidol treating adult patients hospitalized with mild/moderate COVID-19 (ELACOI). MedRxiv. 2020 Jan 1.

Lin S, Shen R, He J, Li X, Guo X. Molecular modeling evaluation of the binding effect of ritonavir, lopinavir and darunavir to severe acute respiratory syndrome coronavirus 2 proteases. bioRxiv. 2020 Jan 1.

Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, Graham BS, McLellan JS. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020 Mar 13;367(6483):1260-3.

Chen WH, Strych U, Hotez PJ, Bottazzi ME. The SARS-CoV-2 vaccine pipeline: an overview. Current tropical medicine reports. 2020 Mar 3:1-4.

Watanabe Y, Allen JD, Wrapp D, McLellan JS, Crispin M. Site-specific analysis of the SARS-CoV-2 glycan shield. BioRxiv. 2020 Jan 1.

McKee DL, Sternberg A, Stange U, Laufer S, Naujokat C. Candidate drugs against SARS-CoV-2 and COVID-19. Pharmacological Research. 2020 Apr 29:104859.

Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, Wang Q, Xu Y, Li M, Li X, Zheng M. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharmaceutica Sinica B. 2020 Feb 27.

Dhama K, Sharun K, Tiwari R, Dadar M, Malik YS, Singh KP, Chaicumpa W. COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics. Human vaccines & immunotherapeutics. 2020 Mar 19:1-7.

Liu C, Zhou Q, Li Y, Garner LV, Watkins SP, Carter LJ, Smoot J, Gregg AC, Daniels AD, Jervey S, Albaiu D. Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases.

Nile SH, Nile A, Qiu J, Li L, Jia X, Kai G. COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons. Cytokine & Growth Factor Reviews. 2020 May 7.

Tolouian R, Vahed SZ, Ghiyasvand S, Tolouian A, Ardalan M. COVID-19 interactions with angiotensin-converting enzyme 2 (ACE2) and the kinin system; looking at a potential treatment. Journal of Renal Injury Prevention. 2020 Mar 30;9(2):e19-.

Kickbusch I, Leung G. Response to the emerging novel coronavirus outbreak.

Bernard K, Thannickal VJ. NADPH Oxidase Inhibition in Fibrotic Pathologies. Antioxidants & Redox Signaling. 2020 Mar 4.

Altarejo Marin T, Machado Bertassoli B, Alves de Siqueira de Carvalho A, Feder D. The use of aliskiren as an antifibrotic drug in experimental models: A systematic review. Drug Development Research. 2020 Feb;81(1):114-26.

Marceau F, Regoli D. Bradykinin receptor ligands: therapeutic perspectives. Nature reviews Drug discovery. 2004 Oct;3(10):845-52.

Xu D, Ma M, Xu Y, Su Y, Ong SB, Hu X, Chai M, Zhao M, Li H, Chen Y, Xu X. Single-cell Transcriptome Analysis Indicates New Potential Regulation Mechanism of ACE2 and NPs signaling among heart failure patients infected with SARS-CoV-2. medRxiv. 2020 Jan 1.

Coskun AK, Yigiter M, Oral A, Odabasoglu F, Halici Z, Mentes O, Cadirci E, Atalay F, Suleyman H. The effects of Montelukast on antioxidant enzymes and proinflammatory cytokines on the heart, liver, lungs, and kidneys in a rat model of cecal ligation and puncture–induced sepsis. TheScientificWorldJOURNAL. 2011 Jan 1;11:1341-56.

Yuan H, Ma Q, Ye L, Piao G. The traditional medicine and modern medicine from natural products. Molecules. 2016 May;21(5):559.

Goothy SS, Goothy S, Choudhary A, Potey GG, Chakraborty H, Kumar AH, Mahadik VK. Ayurveda’s Holistic Lifestyle Approach for the Management of Coronavirus disease (COVID-19): Possible Role of Tulsi. International Journal of Research in Pharmaceutical Sciences. 2020 Mar 20;11(SPL1):16-8.

Srivastava AK, Kumar A, Misra N. On the Inhibition of COVID-19 Protease by Indian Herbal Plants: An In Silico Investigation. arXiv preprint arXiv:2004.03411. 2020 Apr 5.

Vellingiri B, Jayaramayya K, Iyer M, Narayanasamy A, Govindasamy V, Giridharan B, Ganesan S, Venugopal A, Venkatesan D, Ganesan H, Rajagopalan K. COVID-19: A promising cure for the global panic. Science of The Total Environment. 2020 Apr 4:138277.

Shen M, Zhou Y, Ye J, Al-Maskri AA, Kang Y, Zeng S, Cai S. Recent advances and perspectives of nucleic acid detection for coronavirus. Journal of Pharmaceutical Analysis. 2020 Mar 1.

Nguyen T, Duong Bang D, Wolff A. 2019 novel coronavirus disease (COVID-19): paving the road for rapid detection and point-of-care diagnostics. Micromachines. 2020 Mar;11(3):306.

Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK, Bleicker T, Brünink S, Schneider J, Schmidt ML, Mulders DG. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Eurosurveillance. 2020 Jan 23;25(3):2000045.

Xiao Y, Peng Z, Tan C, Meng X, Huang X, Wu A, Li C. Diagnostic Options for Coronavirus Disease 2019 (COVID-19). Infection Control & Hospital Epidemiology. 2020 Apr 23:1-6.

Rubin EJ, Baden LR, Morrissey S, Campion EW. Medical journals and the 2019-nCoV outbreak. N Engl J Med. 2020 Feb 27;382(866):10-56.

Corman VM, Rasche A, Baronti C, Aldabbagh S, Cadar D, Reusken CB, Pas SD, Goorhuis A, Schinkel J, Molenkamp R, Kümmerer BM. Clinical comparison, standardization and optimization of Zika virus molecular detection. Bull. World Health Organ. 2016 Apr 19;829:27.

Long C, Xu H, Shen Q, Zhang X, Fan B, Wang C, Zeng B, Li Z, Li X, Li H. Diagnosis of the Coronavirus disease (COVID-19): rRT-PCR or CT?. European journal of radiology. 2020 Mar 25:108961.

Lamb LE, Bartolone SN, Ward E, Chancellor MB. Rapid Detection of Novel Coronavirus (COVID19) by Reverse Transcription-Loop-Mediated Isothermal Amplification. Available at SSRN 3539654. 2020 Feb 14.

Kellam P, Barclay W. The dynamics of humoral immune responses following SARS-CoV-2 infection and the potential for reinfection. Journal of General Virology. 2020 May 20:jgv001439.

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 research. 2020 Apr 1;176:104742.

Parnham MJ, Nijkamp FP, Rossi AG, editors. Nijkamp and Parnham's Principles of Immunopharmacology. Springer Nature; 2019 Dec 10.