Has spike protein of SARS-CoV-2 mutated significantly since it was first reported in China at the end of 2019? .A systematic review

Abstract

Background and Aims Currently, the global pandemic caused by SARS-CoV-2 is continuing to spread rapidly. Different investigations have attempted to understand the origin of the virus and how this pandemic began. Due to the RNA nature of this virus, it continues to mutate because of a lack of proofreading capability in addition to recombination features and selection pressure. We conducted this systematic review to explore and appraise pooled reliable evidence in all published and non-published studies for determination of the effects of spike mutations in terms of protein functions, transmissibility, pathogenicity and immune escape. Methods We electronically searched the PubMed, Ovid EMBASE and MEDLINE databases from 1 January to 31 June 2020, while medRxiv and bioRxiv were searched from 1 January to 1 June 2020. The PRISMA guidelines and modified STROBE tools were followed in appraising the quality of the studies. Comprehensive criteria were applied to determine the relevancy of any article that included spike mutation testing. In total, 31 works of literature from all regions were analyzed for key significant outcomes, which are described in this systematic review. Results Across all included studies, the overall quality was acceptable for qualitative synthesis. Most of the articles were molecular or molecular epidemiological in nature in that they used varied biotechnological techniques to test mutations. The results identified 15 analyzed mutations within spike proteins that were addressed to change the virus functions: D614G, R408I, V483A, V367F, G476S, S247R, A930V, N439K, S438F, G1124V, P384L, D1168H, V622I, F456L, H1168H, V622I, and F456L. The frequency of these mutations was varied, with the most frequent one being D614G, which was found in 63% of all available sequences. Despite some contradiction among the studies, D614G was reported to increase ACE2-RBD affinity, transmissibility, and pathogenicity and thus might reduce the efficacy of vaccines. In contrast, R408I decreased the receptors’ ACE2 affinity, transmissibility and antibody affinity. There are disagreements among the studies regarding the other spike mutations. Interpretation We could not confirm an overall connection between the D614G mutation and pathogenicity or a reduction in antibody affinity. Nonetheless, our results strongly suggest that the D614G mutation has an impact on ACE2-RBD interactions and thus increases transmissibility. Notwithstanding the limited data, in terms of the RBD mutations, the R408I might have the capability to reduce vaccine effectiveness, but further studies are required. Future well-designed studies and surveillance across the world are needed to better interpret the association between the spike mutations’ effects in the laboratory and the clinical evidence.