The devastating outbreak of COVID-19 has spread all over the world and has become a global health concern. There is no specific therapeutics to encounter the COVID-19. Small interfering RNA (siRNA)-based therapy is an efficient strategy to control human viral infections employing post-transcriptional gene silencing (PTGS) through neutralizing target complementary mRNA. RNA-dependent RNA polymerase (RdRp) encoded by the viral
RdRp
gene as a part of the replication-transcription complex can be adopted as an acceptable target for controlling SARS-CoV-2 mediated infection. Therefore, in the current study, accessible siRNA designing tools, including significant algorithms and parameters, were rationally used to design the candidate siRNAs against SARS-COV-2 encoded
RdRp
. The designed siRNA molecules possessed adequate nucleotide-based and other features for potent gene silencing. The targets of the designed siRNAs revealed no significant matches within the whole human genome, ruling out any possibilities for off-target silencing by the siRNAs. Characterization with different potential parameters of efficacy allowed selecting the finest siRNA among all the designed siRNA molecules. Further, validation assessment and target site accessibility prediction also rationalized the suitability of this siRNA molecule. Molecular docking study between the selected siRNA molecule and component of RNA interference (RNAi) pathway gave an excellent outcome. Molecular dynamics of two complexes: siRNA and argonaute complex, guide RNA, and target protein complex, have shown structural stability of these proteins. Therefore, the designed siRNA molecule might act as an effective therapeutic agent against the SARS-CoV-2 at the genome level and can prevent further outbreaks of COVID-19 in humans.
Since early 2020, the entire world has been facing a disastrous outbreak of the SARS-CoV-2 virus, with massive reporting of death and infections per day. Medical practitioners adopted certain measures such as convalescent plasma therapy, antibody treatment, and injecting vaccines to eradicate the pandemic. In this review, we have primarily focused on the neutralizing antibodies presently under pre-clinical and clinical trials, focusing on their structures, binding affinity, mechanism of neutralization, and advantages over other therapeutics. We have also enlisted all the nAbs against SARS-CoV-2 and its emerging variants in different phases of clinical trials (phase-1, phase-II, and phase-III). The efficacy of administering antibody cocktails over the normal antibodies and their efficacy for the mutant variants of the SARS-CoV-2 virus in minimizing viral virulence is discussed. The potent neutralizing antibodies have eliminated many of the common problems posed by several other therapeutics. A common mechanism of the antibodies and their relevant sources have also been listed in this review.
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