Mutations Observed in the SARS-CoV-2 Spike Glycoprotein and Their Effects in the Interaction of Virus with ACE-2 Receptor

Abstract

Coronaviruses (CoVs) classified in the Coronaviridae family infect a very large spectrum of vertebrate group. Seven CoVs that cause human disease consist of Alpha-CoVs, which are HCoV-229E, and NL63 and beta-CoVs, which are MERS-CoV, SARS-CoV, HCoV-OC43, HCoV-HKU1, and SARS-CoV-2. SARS-CoV-2 is an enveloped, positive-polarity, single-stranded RNA virus responsible for a new Coronavirus disease 2019 (COVID-19). The mutagenic ability of the SARS-CoV-2 directs its evolution and genome variability, thus allowing viruses to escape from host immunity and develop drug resistance. Tracing viral mutations is also important for the development of new vaccines, antiviral drugs, and diagnostic systems. During replication in the host cell, genomic mutations occur in the virus and these mutations are transferred to new generations. For this reason, systematic monitoring of mutations in the SARS-CoV-2 genome allows observation of the national and international molecular epidemiology of the virus. SARS-CoV-2 spike (S) glycoprotein is vital in the binding of the virus to the host cell receptor that is angiotensin converting-enzyme 2 (ACE2), membrane fusion, vaccine studies and immune response to the virus. Therefore, mutations in the gene encoding the S glycoprotein and especially the possible variations in the receptor binding domain (RBD) in S gene are important issues to be emphasized. In this article, information about the mutations observed in the SARS-CoV-2 S glycoprotein and their possible effects are presented.

Scalable live-attenuated SARS-CoV-2 vaccine candidate demonstrates preclinical safety and efficacy

“…Live attenuated vaccines (LAVs) are particularly attractive, as they activate all branches of the host immune system (humoral, innate, and cellular) (2,3). Also, a vaccine that can present all SARS-CoV-2 antigens to the host is optimal because it can both induce a broad immune response and is less likely to lose significant potency due to the antigenic drift that we are already witnessing (4)(5)(6).…”

An Algorithm to Predict the Possible SARS-CoV-2 Mutations

“…The first mutations registered after the initial outbreak in Wuhan are analyzed, i.e. : Y28, A67, N74, W152, Y200, R273, F275, L276, E298, K300, T302, G485, A570, D614, A653, L752, P812, I818, G838, F1103, and V1104 [7][8][9][10][11]. In addition, to corroborate whether the two variants registered in Brazil (until February 2021) could be predicted with the results of the paper, the E484K mutation was initially registered in a patient infected in Rio of Janeiro in October 2020 [3], and later a pool of mutations that occurred in the second Brazilian variant (also known as P. [3].…”

Developmental Status of the Potential Vaccines for the Mitigation of the COVID-19 Pandemic and a Focus on the Effectiveness of the Pfizer-BioNTech and Moderna mRNA Vaccines

“…CRISPR RNAs (crRNAs) can target the SARS-CoV-2 conserved genomic regions, and a bioinformatic analysis by Abbott et al showed that a group of only six crRNAs were more than 90% effective as anti-SARS-CoV-2 agents even though the synthesized fragments were used [ 24 ]. However, it is speculated that the RNAi therapy or the CRISPR-based therapy would be useful if new mutations arise in the viral spike protein-encoding genomes (already 15 amino acid variations have been observed in the RBD of the mutant SARS-CoV-2) which may render the mRNA vaccines or the DNA vaccines inactive against the new strains of SARS-CoV-2 [ 25 , 26 ]. Extensive clinical trials using these two new approaches would be required to prove such an assumption though.…”