Can proteomics-based approaches further help COVID-19 prevention and therapy?

Abstract

The first patient with coronavirus disease (COVID-19) was reported in December 2019 in Wuhan, Hubei province, China. Since then, more than 149.471 million COVID-19 cases have been reported worldwide, with over 3.15 million deaths. The rapid spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection or COVID-19 has made researchers focus on developing an effective vaccine to prevent the disease. One hundred and eighty-four vaccine candidates in pre-clinical development have been tested on different animal models of SARS-CoV-2 infection (Source WHO; Draft landscape and tracker of COVID-19 candidate vaccines (who.int)). An additional 63 vaccines are currently in clinical development. Thus, more than 200 vaccine candidates have been developed within almost a year of the first reported case of COVID-19, and of these, 10 vaccines have been approved for human use (Table 1). The first human trial of a COVID-19 vaccine started on 6 March 2020, and the rapid pace of vaccine development would not have been feasible without a combined proteomics and genomics approach against SARS-CoV-2. The recent emergence of SARS-CoV-2 variants in the United Kingdom (known as 20I/501Y.V1, VOC 202,012/01, or B.1.1.7), South Africa (20 H/501Y.V2 or B.1.351), and Brazil (P.1 B.1.1.28. P1 or 20 J/501Y.V3; this variant has unique mutations, including three in the receptor-binding domains [RBDs] of the spike [S] protein) is of marked concern for vaccine efficacy against COVID-19 (Figure 1). The B.1.1.7 variant, originating in the United Kingdom, has now spread globally. Infected patients induce a defective antibody (Ab) response that is unable to protect against the parent SARS-CoV-2 or its B.1.351 variant, indicating the induction of asymmetric heterotypic immunity [1]. Mutant strains have also emerged in the USA. For example, the SARS-CoV-2 variant, CAL.20 C, discovered in Southern California has three mutations in its S-protein, characterizing it as a subclade of 20 C, and the S protein L452R mutation in the RBD makes it resistant to several S protein monoclonal Abs [2,3]. Mutant strains of SARS-CoV-2 are of great concern in terms of the efficacy of currently available vaccines. For example, SARS-CoV-2 S protein variants can escape the action of neutralizing Abs or may be less efficiently cleared [4,5]. The vaccine developed by Pfizer for COVID-19 has a low efficacy against the South African variant P.1. The vaccine developed by Novavax (NVX-CoV2373) is 50–60% less effective against the South African variant but has a high efficacy against the UK variant [6]. The 501Y.V2 or B.1.351 variants also escape neutralization by convalescent plasma, indicating that the mutant virus can evade the immunity generated by prior SARS-CoV-2 infection [7]. Thus, emerging SARS-CoV-2 variants that can escape approved vaccine-based immune responses and convalescent plasma-based therapies are of concern. Depending on the severity of COVID-19, patients receive a combination of different drugs, including antivirals (favipiravir), antimalarials (hydroxychloroquine), antibacterials (azithromycin and doxycycline), antiplatelets, and immunomodulators [8–10]. In November 2020, the World Health Organization approved the antiviral, Remdesivir (previously used for treating hepatitis C virus and Ebola virus infections), as a conditional drug. It is not possible to mention all the clinical trials associated with COVID-19 therapy. However, AstraZeneca’s Calquence (a blood cancer drug) failed in phase 2 trial, Novartis’ Ilaris (an anti-arthritis drug) showed no benefit to COVID-19 patients, and Sanofi and Regeneron’s Kevzara (a drug used for treating rheumatoid arthritis) did not perform favorably in COVID-19 patients.