Investigation of the changes that can be occurred in the protein structure caused by SARS-CoV-2 non-structural protein-13 (helicase) mutations

Corona Virus Disease 2019 is a viral disease in which severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) is the pathological agent. SARS-CoV-2 helicase (non-structural protein-13) has a vital role in the process of replication of the viral genome. SARS-CoV-2 helicase is at the center of antiviral drug studies to be developed to suppress viral replication. Mutations may affect the course of the disease and the responses of antivirals by causing changes in protein structure and stability. In this study, the changes that mutations in nsp13, which encodes the SARS-CoV-2 helicase protein, may cause in protein structure and stability were investigated in order to contribute to the understanding of the course of the disease and the development of valid antivirals. The sequence data of 1616 European, and 2483 American isolates infected with the SARS-CoV-2 virus were compiled using Mega XI software. Seven mutations (Ser36Pro,Thr127Asn,His164Tyr, Met233Ile,Ala368Val,Ala389Val,Thr599Ile) in American isolates, two mutations (Pro77Leu, Gly170Ser) in European isolates, and two mutations (Tyr324Cys,Arg394Cys) common to both isolates were identified. Mutant protein structures were modeled with the Robetta tool. Model quality was evaluated using Molprobity and QMEAN tools. The model quality scores were found to be within the acceptable range. The effects of mutations on protein structure and stability were analyzed using SDM2, mCSM, DUET and DynaMut2 tools. Ten of these mutations (Ser36Pro,Pro77Leu,Thr127Asn, Gly170Ser, Met233Ile,Thr324Cys,Ala368Val,Ala389Val,Arg392Cys,Thr599Ile) caused a decrease in protein stability (-4.37≤ ΔΔGstability≤-0.005), while one of them (His164Tyr) resulted in increased protein stability (0.003≤ ΔΔGstability≤1.51). Consequently, topological and stability changes in nsp13 may lead to changes in the effectiveness of therapeutics. Different mutations for nsp13 of SARS-CoV-2 seen in European and American isolates may lead to the emergence of different phenotypes in terms of viral activity. Different treatment approaches in different geographical regions can make the fight against the virus successful.