Background: Coronavirus disease 2019 (COVID-19) has rapidly spread worldwide, but safe and effective treatment options remain unavailable. Numerous systematic reviews of varying qualities have tried to summarize the evidence on the available therapeutic interventions for COVID-19. This overview of reviews aims to provide a succinct summary of the findings of systematic reviews on different pharmacological and non-pharmacological therapeutic interventions for COVID-19. Methods: We searched PubMed, Embase, Google Scholar, Cochrane Database of Systematic Reviews, and WHO database of publications on COVID-19 from 1 December 2019 through to 11 June 2020 for peer-reviewed systematic review studies that reported on potential pharmacological or non-pharmacological therapies for COVID-19. Quality assessment was completed using A MeaSurement Tool to Assess systematic Reviews-2 (AMSTAR-2) measure. Results: Out of 816 non-duplicate studies, 45 were included in the overview. Antiviral and antibiotic agents, corticosteroids, and anti-malarial agents were the most common drug classes used to treat COVID-19; however, there was no direct or strong evidence to support their efficacy. Oxygen therapy and ventilatory support was the most common non-pharmacological supportive care. The quality of most of the included reviews was rated as low or critically low. Conclusion: This overview of reviews demonstrates that although some therapeutic interventions may be beneficial to specific subgroups of COVID-19 patients, the available data are insufficient to strongly recommend any particular treatment option to be used at a population level. Future systematic reviews on COVID-19 treatments should adhere to the recommended systematic review methodologies and ensure that promptness and comprehensiveness are balanced. The reviews of this paper are available via the supplemental material section.
Background: Mutations in the SARS-CoV-2 genome might influence pathogenicity, transmission rate, and evasion of the host immune system. Therefore, the purpose of this study was to assess the genetic alteration in the receptor binding domain (RBD) of the spike and putative RNA binding site of the RdRp genes of SARS-CoV-2.
Materials and Method: In this cross-sectional study, 45 confirmed COVID-19 patients using qRT-PCR were included and divided into mild, severe, and critical groups based on the severity of the disease. RNA was extracted from nasopharyngeal swab samples using a commercial kit. RT-PCR was performed to amplify the target sequences of the spike and RdRp genes and sequenced them by the Sanger method. Clustal OMEGA, MEGA 11 software, I-mutant tools, and SWISS-MODEL and HDOCK web servers were used for bioinformatics analyses.
Results: The mean age of the patients was 50.68±2.73. The results showed that four of six mutations (L452R, T478K, N501Y, and D614G) in RBD and three of eight in the putative RNA binding site (P214L, E1084D, V1883T) were missense. In the putative RNA binding site, another deletion was discovered. Among missense mutations, N501Y and V1883T were responsible for increasing structural stability, and the others were responsible for decreasing it. The various homology models designed showed that these homologies were like the Wuhan model. The molecular docking analysis revealed that the T478K mutation in RBD had the highest binding affinity. In addition, 35 RBD samples (89.7%) and 33 putative RNA binding site samples (84.6%) were similar to the Delta variant.
Conclusion: Our results indicated that double mutations (T478K and N501Y) in the S protein might increase the binding affinity of SARS-CoV-2 to human ACE2 compared to the wild type (WT) strain. Moreover, variations in the spike and RdRp genes might influence the stability of encoded proteins.
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