Can we Succeed in the Fight Against SARS-CoV-2 with its Emerging New Variants?

Shima      Tavakol; Hani      Tavakol; Mo   S.   Alavijeh; Alexander      Seifalian
Abstract

In 2019, the whole world came together to confront a life-threatening virus named SARS-CoV-2, causing COVID-19 illness. The virus infected the human host by attaching to the ACE2 and CD147 receptors in some human cells, resulting in cytokine storm and death. The new variants of the virus that caused concern are Alpha, Beta, Gamma, Delta, and Epsilon, according to the WHO label. However, Pango lineages designated them as B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.429. Variants may be progressively formed in one chronic COVID-19 patient and transmitted to others. They show some differences in cellular and molecular mechanisms. Mutations in the receptor-binding domain (RBD) and N-terminal domain (NTD) lead to alterations in the host's physiological responses. They show significantly higher transmissibility rates and viral load while evading neutralizing antibodies at different rates. These effects are through mutations, deletion, and conformational alterations in the virus, resulting in the enhanced affinity of RBD to PD of ACE2 protein, virus entry, and spike conformational change. In the clinical laboratory, new variants may diagnose from other variants using specific primers for RBD or NTD. There are some controversial findings regarding the efficacy of the developed vaccines against the new variants. This research aimed to discuss the cellular and molecular mechanisms beyond COVID-19 pathogenesis, focusing on the new variants. We glanced at why the mutations and the ability to transmit the virus increase and how likely the available vaccines will be effective against these variants.
Keywords: SARS-CoV-2, COVID-19, vaccine, variant of concern, mutations, transmissibility rate.
[1]
Tavakol S, Tavakol H, Alavijeh MS, Seifalian A. The world against versatile SARS-Cov-2 nanomachines: Mythological or reality? Curr Stem Cell Res Ther  2022; 17(1): 43-57.
 [http://dx.doi.org/10.2174/1574888X16666210712213102] [PMID: 34254928]

[2]
Sexton NR, Smith EC, Blanc H, Vignuzzi M, Peersen OB, Denison MR. Homology-based identification of a mutation in the coronavirus RNA-dependent RNA polymerase that confers resistance to multiple mutagens. J Virol  2016; 90(16): 7415-28.
 [http://dx.doi.org/10.1128/JVI.00080-16] [PMID: 27279608]

[3]
Drexler JF, Gloza-Rausch F, Glende J, et al. Genomic characterization of severe acute respiratory syndrome-related coronavirus in European bats and classification of coronaviruses based on partial RNA-dependent RNA polymerase gene sequences. J Virol  2010; 84(21): 11336-49.
 [http://dx.doi.org/10.1128/JVI.00650-10] [PMID: 20686038]

[4]
WHO. Tracking SARS-CoV-2 variants 2021.

[5]
Li G, De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat Rev Drug Discov  2020; 19(3): 149-50.

[6]
Cascella M, Michael R, Arturo C, Dulebohn SC, Napoli RD. Features, evaluation and treatment Coronavirus (COVID-19) Treasure Island. FL: StatPearls Publishing 2010.

[7]
Gralinski LE, Menachery VD. Return of the Coronavirus: 2019-nCoV. Viruses  2020; 12(2): 135.
 [http://dx.doi.org/10.3390/v12020135] [PMID: 31991541]

[8]
Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinical-ly proven protease inhibitor. Cell  2020; 181(2): 271-280.e8.
 [http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]

[9]
Yu H, Li D, Deng Z, et al. Total protein as a biomarker for predicting coronavirus disease-2019 pneumonia 2020.
 [http://dx.doi.org/10.2139/ssrn.3551289]

[10]
Chan JF-W, Kok K-H, Zhu Z, et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect  2020; 9(1): 221-36.
 [http://dx.doi.org/10.1080/22221751.2020.1719902] [PMID: 31987001]

[11]
Zhou P, Yang X-L, Wang X-G, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature  2020; 579: 270-3.

[12]
Matsuyama S, Nagata N, Shirato K, Kawase M, Takeda M, Taguchi F. Efficient activation of the severe acute respiratory syndrome coro-navirus spike protein by the transmembrane protease TMPRSS2. J Virol  2010; 84(24): 12658-64.
 [http://dx.doi.org/10.1128/JVI.01542-10] [PMID: 20926566]

[13]
Shulla A, Heald-Sargent T, Subramanya G, Zhao J, Perlman S, Gallagher T. A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry. J Virol  2011; 85(2): 873-82.
 [http://dx.doi.org/10.1128/JVI.02062-10] [PMID: 21068237]

[14]
Belouzard S, Chu VC, Whittaker GR. Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites. Proc Natl Acad Sci USA  2009; 106(14): 5871-6.
 [http://dx.doi.org/10.1073/pnas.0809524106] [PMID: 19321428]

[15]
Millet JK, Whittaker GR. Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis. Virus Res  2015; 202: 120-34.
 [http://dx.doi.org/10.1016/j.virusres.2014.11.021] [PMID: 25445340]

[16]
Simmons G, Gosalia DN, Rennekamp AJ, Reeves JD, Diamond SL, Bates P. Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Proc Natl Acad Sci USA  2005; 102(33): 11876-81.
 [http://dx.doi.org/10.1073/pnas.0505577102] [PMID: 16081529]

[17]
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): e01815-8.
 [http://dx.doi.org/10.1128/JVI.01815-18] [PMID: 30626688]

[18]
Shirato K, Kawase M, Matsuyama S. Wild-type human coronaviruses prefer cell-surface TMPRSS2 to endosomal cathepsins for cell entry. Virology  2018; 517: 9-15.
 [http://dx.doi.org/10.1016/j.virol.2017.11.012] [PMID: 29217279]

[19]
Zhou Y, Vedantham P, Lu K, et al. Protease inhibitors targeting coronavirus and filovirus entry. Antiviral Res  2015; 116: 76-84.
 [http://dx.doi.org/10.1016/j.antiviral.2015.01.011] [PMID: 25666761]

[20]
Jia HP, Look DC, Tan P, et al. Ectodomain shedding of angiotensin converting enzyme 2 in human airway epithelia. Am J Physiol Lung Cell Mol Physiol  2009; 297(1): L84-96.
 [http://dx.doi.org/10.1152/ajplung.00071.2009] [PMID: 19411314]

[21]
Xiao F, Zimpelmann J, Burger D, Kennedy C, Hébert RL, Burns KD. Protein kinase C-δ mediates shedding of angiotensin-converting enzyme 2 from proximal tubular cells. Front Pharmacol  2016; 7: 146.
 [http://dx.doi.org/10.3389/fphar.2016.00146] [PMID: 27313531]

[22]
Eren E, Aydin M, Sarkaya C, Yilmaz N. Hypothetical overview of possible associations between iron metabolism and neurodegenerative disorders in COVID-19 patients. Project: Covid-19 and iron metabolism 2020.
 [http://dx.doi.org/10.13140/RG.2.2.28070.96329]

[23]
Islam MR, Hoque MN, Rahman MS, et al. Genome-wide analysis of SARS-CoV-2 virus strains circulating worldwide implicates hetero-geneity. Sci Rep  2020; 10(1): 14004.
 [http://dx.doi.org/10.1038/s41598-020-70812-6] [PMID: 32814791]

[24]
Rambaut A, Loman N, Pybus O, et al. Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations 2020. Available from: www.virological.org

[25]
Contro ECfDPa. Rapid increase of a SARS-CoV-2 variant with multiple spike protein mutations observed in the United Kingdom ECDC. Stockholm 2020.

[26]
CDC. Emerging SARS-CoV-2 Variants 2021. Available from: https://stacks.cdc.gov

[27]
Young BE, Fong S-W, Chan Y-H, et al. Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: An observational cohort study. Lancet  2020; 396(10251): 603-11.
 [http://dx.doi.org/10.1016/S0140-6736(20)31757-8] [PMID: 32822564]

[28]
Fiorentini S, Messali S, Zani A, et al. First detection of SARS-CoV-2 spike protein N501 mutation in Italy in August, 2020. Lancet Infect Dis  2021; 21(6): e147.
 [http://dx.doi.org/10.1016/S1473-3099(21)00007-4] [PMID: 33450180]

[29]
Bloomberg JG. Alpha bad, Delta worse—and Lambda? Why each new COVID variant causes so much alarm Fortune 2021. Available from: https://fortune.com

[30]
Weisblum Y, Schmidt F, Zhang F, et al. Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. eLife  2020; 9: e61312.
 [http://dx.doi.org/10.7554/eLife.61312] [PMID: 33112236]

[31]
Tsang HF, Yu ACS, Wong HT, et al. Whole genome amplicon sequencing and phylogenetic analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from lineage B. 1.36. 27 isolated in Hong Kong. Expert Rev Mol Diagn  2021; 1: 119-24.
 [PMID: 34878349]

[32]
Resende PC, Bezerra JF. RHT dV Spike E484K mutation in the first SARS-CoV-2 reinfection case confirmed in Brazil, 2020 external icon 2021. Available from: www.virological.org

[33]
Starr TN, Greaney AJ, Dingens AS, Bloom JD. Complete map of SARS-CoV-2 RBD mutations that escape the monoclonal antibody LY-CoV555 and its cocktail with LY-CoV016. Cell Rep Med  2021; 2(4): 100255.
 [http://dx.doi.org/10.1016/j.xcrm.2021.100255] [PMID: 33842902]

[34]
Shen X, Tang H, Pajon R, et al. Neutralization of SARS-CoV-2 variants B. 1.429 and B. 1.351. N Engl J Med  2021; 384(24): 2352-4.
 [http://dx.doi.org/10.1056/NEJMc2103740] [PMID: 33826819]

[35]
McCallum M, Bassi J, De Marco A, et al. SARS-CoV-2 immune evasion by variant B. 1.427/B. 1.429. BioRxiv 2021.
 [http://dx.doi.org/10.1101/2021.03.31.437925]

[36]
Koyama T, Platt D, Parida L. Variant analysis of SARS-CoV-2 genomes. Bull World Health Organ  2020; 98(7): 495-504.
 [http://dx.doi.org/10.2471/BLT.20.253591] [PMID: 32742035]

[37]
Conti P, Caraffa A, Gallenga CE, et al. The British variant of the new coronavirus-19 (Sars-Cov-2) should not create a vaccine problem. J Biol Regul Homeost Agents  2021; 35(1): 1-4.
 [PMID: 33377359]

[38]
Butowt R, Bilinska K, Von Bartheld CS. Chemosensory dysfunction in COVID-19: Integration of genetic and epidemiological data points to D614G spike protein variant as a contributing factor. ACS Chem Neurosci  2020; 11(20): 3180-4.
 [http://dx.doi.org/10.1021/acschemneuro.0c00596] [PMID: 32997488]

[39]
Yurkovetskiy L, Wang X, Pascal KE, et al. Structural and functional analysis of the D614G SARS-CoV-2 spike protein variant. Cell  2020; 183: 739-51.

[40]
Plante JA, Liu Y, Liu J, et al. Spike mutation D614G alters SARS-CoV-2 fitness. Nature  2021; 592(7852): 116-21.
 [PMID: 33106671]

[41]
Hudson BS, Kolte V, Khan A, Sharma G. Dynamic tracking of variant frequencies depicts the evolution of mutation sites amongst SARS‐CoV‐2 genomes from India. J Med Virol  2021; 93(4): 2534-7.
 [PMID: 33368386]

[42]
Yurkovetskiy L, Pascal KE, Tomkins-Tinch C, et al. SARS-CoV-2 Spike protein variant D614G increases infectivity and retains sensitivity to antibodies that target the receptor binding domain. bioRxiv 202 

[43]
Baric RS. Emergence of a highly fit SARS-CoV-2 variant. N Engl J Med  2020; 383(27): 2684-6.
 [http://dx.doi.org/10.1056/NEJMcibr2032888] [PMID: 33326716]

[44]
Klumpp-Thomas C, Kalish H, Hicks J, et al. D614G spike variant does not alter IgG, IgM, or IgA spike seroassay performance. medRxiv 2020.
 [http://dx.doi.org/10.1101/2020.07.08.20147371]

[45]
Borges V, Isidro J, Cortes-Martins H, et al. Massive dissemination of a SARS-CoV-2 Spike Y839 variant in Portugal. Emerg Microbes Infect  2020; 9(1): 2488-96.
 [http://dx.doi.org/10.1080/22221751.2020.1844552] [PMID: 33131453]

[46]
Sun Y-S, Xu F, An Q, et al. A SARS-CoV-2 variant with the 12-bp deletion at E gene. Emerg Microbes Infect  2020; 9(1): 2361-7.
 [http://dx.doi.org/10.1080/22221751.2020.1837017] [PMID: 33118859]

[47]
Caccuri F, Zani A, Messali S, et al. A persistently replicating SARS-CoV-2 variant derived from an asymptomatic individual. J Transl Med  2020; 18(1): 362.
 [http://dx.doi.org/10.1186/s12967-020-02535-1] [PMID: 32967693]

[48]
Konno Y, Kimura I, Uriu K, 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.
 [http://dx.doi.org/10.1016/j.celrep.2020.108185] [PMID: 32941788]

[49]
Haga S, Yamamoto N, Nakai-Murakami C, et al. Modulation of TNF-α-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-α production and facilitates viral entry. Proc Natl Acad Sci USA  2008; 105(22): 7809-14.
 [http://dx.doi.org/10.1073/pnas.0711241105] [PMID: 18490652]

[50]
Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med  2005; 11(8): 875-9.
 [http://dx.doi.org/10.1038/nm1267] [PMID: 16007097]

[51]
Glowacka I, Bertram S, Herzog P, et al. Differential downregulation of ACE2 by the spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus NL63. J Virol  2010; 84(2): 1198-205.
 [http://dx.doi.org/10.1128/JVI.01248-09] [PMID: 19864379]

[52]
Sahin AR, Erdogan A, Agaoglu PM, et al. 2019 novel Coronavirus (COVID-19) outbreak: a review of the current literature. EJMO  2020; 4: 1-7.
 [http://dx.doi.org/10.14744/ejmo.2020.12220]

[53]
Zimmermann P, Curtis N. Coronavirus infections in children including COVID-19. Pediatr Infect Dis J  2020; 39(5): 355-68.
 [http://dx.doi.org/10.1097/INF.0000000000002660]

[54]
Team TNCPERE. The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19)—China, 2020. Zhonghua Liu Xing Bing Xue Za Zhi  2020; 41(2): 145-51.

[55]
Jernigan DB. China CDC Weekly 2020 2020. Available from: https://www.scienceopen.com

[56]
Fan C, Li K, Ding Y, Lu WL, Wang J. ACE2 expression in kidney and testis may cause kidney and testis damage after 2019-nCoV infection. medRxiv 2020.
 [http://dx.doi.org/10.1101/2020.02.12.20022418]

[57]
Yin Y, Wunderink RG. MERS, SARS and other coronaviruses as causes of pneumonia. Respirology  2018; 23(2): 130-7.
 [http://dx.doi.org/10.1111/resp.13196] [PMID: 29052924]

[58]
Xia H, Lazartigues E. Angiotensin-converting enzyme 2 in the brain: Properties and future directions. J Neurochem  2008; 107(6): 1482-94.
 [http://dx.doi.org/10.1111/j.1471-4159.2008.05723.x] [PMID: 19014390]

[59]
Doobay MF, Talman LS, Obr TD, Tian X, Davisson RL, Lazartigues E. Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol  2007; 292(1): R373-81.
 [http://dx.doi.org/10.1152/ajpregu.00292.2006] [PMID: 16946085]

[60]
Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 virus targeting the CNS: Tissue distribution, host–virus interaction, and proposed neurotropic mechanisms. ACS Chem Neurosci  2020; 11(7): 995-8.

[61]
Ahmadirad N, Ghasemi Z. COVID-19 and central nervous system: Entry routes and. Basic Clin Neurosci  2020; 11(2): 217-24.
 [http://dx.doi.org/10.32598/bcn.11.covid19.2360.1] [PMID: 32855781]

[62]
Nelson R. Risk variant for Severe COVID-19 inherited from Neanderthals 111 RIVER ST, Hoboken 07030-5774. NJ, USA: Wiley 2020.

[63]
Ghosh R, De K, Roy D, et al. A case of area postrema variant of neuromyelitis optica spectrum disorder following SARS-CoV-2 infection. J Neuroimmunol  2020; 350: 577439.
 [http://dx.doi.org/10.1016/j.jneuroim.2020.577439] [PMID: 33333471]

[64]
Abbaslou MA, Karbasi M, Mozhdehipanah H. A rare axonal variant of Guillain-Barré syndrome as a neurological complication of COVID-19 infection. Arch Iran Med  2020; 23(10): 718-21.
 [http://dx.doi.org/10.34172/aim.2020.93] [PMID: 33107316]

[65]
Lascano AM, Epiney JB, Coen M, et al. SARS-CoV-2 and Guillain-Barré syndrome: AIDP variant with a favourable outcome. Eur J Neurol  2020; 27(9): 1751-3.
 [http://dx.doi.org/10.1111/ene.14368] [PMID: 32478936]

[66]
Caamaño JDS, Beato AR. Facial diplegia, a possible atypical variant of Guillain-Barré syndrome as a rare neurological complication of SARS-CoV-2. J Clin Neurosci  2020; 77: 230-2.
 [http://dx.doi.org/10.1016/j.jocn.2020.05.016] [PMID: 32410788]

[67]
Zhang Y, Qin L, Zhao Y, et al. Interferon-induced transmembrane protein 3 genetic variant rs12252-C associated with disease severity in coronavirus disease 2019. J Infect Dis  2020; 222(1): 34-7.
 [http://dx.doi.org/10.1093/infdis/jiaa224] [PMID: 32348495]

[68]
Tikellis C, Thomas M. Angiotensin-converting enzyme 2 (ACE2) is a key modulator of the renin angiotensin system in health and disease. Int J Pept  2012; 2012: 256294.

[69]
Oniszczuk J, Moktefi A, Mausoleo A, et al. De novo focal and segmental glomerulosclerosis after COVID-19 in a patient with a transplanted kidney from a donor with a high-risk APOL1 variant. Transplantation  2021; 105(1): 206-11.
 [http://dx.doi.org/10.1097/TP.0000000000003432] [PMID: 32852403]

[70]
Zheng Y-Y, Ma Y-T, Zhang J-Y, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol  2020; 17(5): 259-60.
 [http://dx.doi.org/10.1038/s41569-020-0360-5] [PMID: 32139904]

[71]
Alhogbani T. Acute myocarditis associated with novel Middle east respiratory syndrome coronavirus. Ann Saudi Med  2016; 36(1): 78-80.
 [http://dx.doi.org/10.5144/0256-4947.2016.78] [PMID: 26922692]

[72]
Wong CK, Lam CW, Wu AK, et al. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol  2004; 136(1): 95-103.
 [http://dx.doi.org/10.1111/j.1365-2249.2004.02415.x] [PMID: 15030519]

[73]
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet  2020; 395(10223): 497-506.
 [http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]

[74]
Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA  2020; 323(11): 1061-9.

[75]
Sakabe M, Yoshioka R, Fujiki A. Sick sinus syndrome induced by interferon and ribavirin therapy in a patient with chronic hepatitis C. J Cardiol Cases  2013; 8(6): 173-5.
 [http://dx.doi.org/10.1016/j.jccase.2013.08.002] [PMID: 30534284]

[76]
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet  2020; 395(10223): 507-13.
 [http://dx.doi.org/10.1016/S0140-6736(20)30211-7] [PMID: 32007143]

[77]
WHO. Epidemiological update: Occurrence of variants of SARS-CoV-2 in the Americas Pan Am Health Org 2021. Available from https://reliefweb.int/report/brazil/epidemiological-update-occurrence-variants-sars-cov-2-americas-20-january-2021

[78]
Zimmer K. A guide to emerging SARS-CoV-2 variants. Scientist 2021. Available from: https://www.the-scientist.com

[79]
Graham MS, Sudre CH, May A, et al. The effect of SARS-CoV-2 variant B. 1.1. 7 on symptomatology, re-infection and transmissibility. medRxiv 2021.

[80]
Radcliffe S. The COVID-19 delta variant: here’s everything you need to know. Health Care (Don Mills) 2021. Available from: https://www.healthline.com

[81]
Kemp S, Collier D, Datir R, et al. Neutralising antibodies drive Spike mediated SARS-CoV-2 evasion. medRxivbioRxiv 2020.

[82]
Choi B, Choudhary MC, Regan J, et al. Persistence and evolution of SARS-CoV-2 in an immunocompromised host. N Engl J Med  2020; 383(23): 2291-3.
 [http://dx.doi.org/10.1056/NEJMc2031364] [PMID: 33176080]

[83]
Horby P. New and emerging respiratory virus threats advisory group. NERVTAG meeting on SARS-CoV-2 variant under investigation VUI-202012/01 2020.

[84]
Oran DP, Topol EJ. Prevalence of asymptomatic SARS-CoV-2 infection: A narrative review. Ann Intern Med  2020; 173(5): 362-7.
 [http://dx.doi.org/10.7326/M20-3012] [PMID: 32491919]

[85]
Xu H, Xie CY, Li PH, et al. Demographic, virological characteristics and prognosis of asymptomatic COVID-19 patients in South China. Front Med (Lausanne)  2022; 9: 830942.
 [http://dx.doi.org/10.3389/fmed.2022.830942] [PMID: 35155505]

[86]
Garret N, Tapley A, Andriesen J, et al. High rate of asymptomatic carriage associated with variant strain Omicron. MedRxiv 2021.
 [http://dx.doi.org/10.1101/2021.12.20.21268130]

[87]
Reuschl A-K, Thorne L, Alvarez LZ, et al. Host-directed therapies against early-lineage SARS-CoV-2 retain efficacy against B. 1.1. 7 variant bioRxiv 2021.

[88]
Sammartano V, Santoni A, Frediani B, et al. Efficacy and safety of ruxolitinib for COVID-19 related acute respiratory distress syndrome in a patient with blastic plasmacytoid dendritic cell neoplasm (leukemic variant). Leuk Lymphoma  2020; 61(14): 3523-5.
 [http://dx.doi.org/10.1080/10428194.2020.1817440] [PMID: 32902339]

[89]
Tarrytown NY. REGEN-COV™ antibody cocktail is active against SARS-COV-2 variants first identified in the UK and South Africa. Regeneron 2021.

[90]
Loutfy MR, Blatt LM, Siminovitch KA, et al. Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: A preliminary study. JAMA  2003; 290(24): 3222-8.
 [http://dx.doi.org/10.1001/jama.290.24.3222] [PMID: 14693875]

[91]
Lee RB. B117: What we know about the novel SARS-CoV-2 variant Am Soc Microbiol 2021. Available from: https://asm.org/Articles/2021/January/B-1-1-7-What-We-Know-About-the-Novel-SARS-CoV-2-Va

[92]
Starr TN, Greaney AJ, Hilton SK, et al. Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding. Cell  2020; 182: 1295-310.

[93]
Hoffmann M, Kleine-Weber H, Pöhlmann 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: 779-84.

[94]
Zhu Y, Feng F, Hu G, et al. The S1/S2 boundary of SARS-CoV-2 spike protein modulates cell entry pathways and transmission. bioRxiv 2020.
 [http://dx.doi.org/10.1101/2020.08.25.266775]

[95]
Mahase E. Covid-19: What have we learnt about the new variant in the UK? BMJ  2020; 371: m4944.

[96]
Zhang W, Davis BD, Chen SS, Martinez SJM, Plummer JT, Vail E. Emergence of a novel SARS-CoV-2 variant in Southern California. JAMA  2021; 325(13): 1324-6.
 [http://dx.doi.org/10.1001/jama.2021.1612] [PMID: 33571356]

[97]
McLaren TA, Gruden JF, Green DB. The bullseye sign: A variant of the reverse halo sign in COVID-19 pneumonia. Clin Imaging  2020; 68: 191-6.
 [http://dx.doi.org/10.1016/j.clinimag.2020.07.024] [PMID: 32853842]

[98]
McCallum M, De Marco A, Lempp FA, et al. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell  2021; 184: 2332-47.

[99]
Chaudhari AM, Kumar D, Joshi M, Patel A, Joshi C. E156/G and Arg158, Phe-157/del mutation in NTD of spike protein in B.1.167.2 lineage of SARS-CoV-2 leads to immune evasion through antibody escape. BioRxiv 2021.

[100]
Fratev F. The SARS-CoV-2 S1 spike protein mutation N501Y alters the protein interactions with both hACE2 and human derived antibody: A Free energy of perturbation study. bioRxiv 2020.

[101]
McCarthy KR, Rennick LJ, Nambulli S, et al. Natural deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. bioRxiv 2020.

[102]
Thomson EC, Rosen LE, Shepherd JG, et al. The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading anti-body-mediated immunity. bioRxiv 2020.
 [http://dx.doi.org/10.1101/2020.11.04.355842]

[103]
Wang Z, Schmidt F, Weisblum Y, et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. bioRxiv 2021.

[104]
Callaway E. Fast-spreading COVID variant can elude immune responses. Nature  2021; 589(7843): 500-1.
 [http://dx.doi.org/10.1038/d41586-021-00121-z] [PMID: 33479534]

[105]
Gupta R, Collier D, De Marco A, et al. SARS-CoV-2 B. 1.1. 7 escape from mRNA vaccine-elicited neutralizing antibodies. medRxiv 2021.

[106]
Muik A, Wallisch A-K, Sänger B, et al. Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine-elicited hu-man sera. Science  2021; 371(6534): 1152-3.
 [http://dx.doi.org/10.1126/science.abg6105] [PMID: 33514629]

[107]
Tavakol S, Alavijeh MS, Seifalian AM. COVID-19 vaccines in clinical trials and their mode of action for immunity against the virus. Curr Pharm Des  2021; 27(13): 1553-63.
 [http://dx.doi.org/10.2174/1381612826666201023143956] [PMID: 33100195]

[108]
Tavakol S, Zahmatkeshan M, Mohammadinejad R, et al. The role of nanotechnology in current COVID-19 outbreak. Heliyon  2021; 7(4): e06841.
 [http://dx.doi.org/10.1016/j.heliyon.2021.e06841] [PMID: 33880422]

[109]
Pfanner E, Ring E. Astra Shot Shows 82% Efficacy With U.K.’s Two-Dose Interval. Bloomberg 2021. Available from: https://news.bloomberglaw.com/health-law-and-business/astra-vaccine-shows-82-efficacy-with-3-month-gap-oxford-says

[110]
Mahase E. Covid-19: South Africa pauses use of Oxford vaccine after study casts doubt on efficacy against variant. BMJ  2021; 372(n372)

[111]
Novavax.. Novavax COVID-19 Vaccine Demonstrates 893% Efficacyin UK Phase 3 Trial. 2020. Available from: https://mvec.mcri.edu.au/novavax-covid-19-vaccine-demonstrates-89-3-efficacy-in-uk-phase-3-trial/.

[112]
Arthur R. South Africa has started administering the Janssen COVID-19 vaccine to health workers. Biopharma Reporter 2021. Available from: https://www.biopharma-reporter.com/Article/2021/02/18/South-Africa-starts-administering-Janssen-COVID-19-vaccine-to-health-workers.

[113]
Support the Guardian. Johnson & Johnson one-dose COVID] vaccine shown to work 2021. Available from: https://www.theguardian.com/world/2021/may/28/johnson-johnson-single-shot-covid-vaccine-approved-for-use-in-uk

[114]
Bernal JL, Andrews N, Gower C, et al. Effectiveness of COVID-19 vaccines against the B. 1.617. 2 variant. medRxiv 2021.

[115]
Wall EC, Wu M, Harvey R, et al. Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vac-cination. Lancet  2021; 397(10292): 2331-3.
 [http://dx.doi.org/10.1016/S0140-6736(21)01290-3] [PMID: 34090624]

[116]
Davis C, Logan N, Tyson G, et al. Reduced neutralisation of the Delta (B. 1.617. 2) SARS-CoV-2 variant of concern following vaccination. medRxiv 2021.

[117]
Mahase E. Delta variant: What is happening with transmission, hospital admissions, and restrictions? BMJ  2021; 373(n1513)

[118]
McCallum M, Bassi J, De Marco A, et al. SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern. Science  2021; 373(6555): 648-54.
 [http://dx.doi.org/10.1126/science.abi7994] [PMID: 34210893]
Cite As
Current Pharmaceutical Design

Can we Succeed in the Fight Against SARS-CoV-2 with its Emerging New Variants?

Abstract
