Maximum Mismatch between Six-Residue Sequences of SARS-CoV-2 Spike Proteins and Human Proteome

Abstract

A first step toward finding effective antivirals for Covid-19 may be the identification of immunogenic, conserved, short and accessible epitopes on the surface molecules of human coronavirus. An important requirement, however, would be to be sure these epitopes do not align well with human proteins, thereby reducing the possibility of off-target interactions by the antiviral. So far, the focus of the medical and scientific communities has been on finding vaccines that can combat the disease preemptively, but this approach might fall short upon the next mutation of the virus. Would there be a safe and sustainable treatment strategy for a viral infection such as Covid-19 when new variants or strains of the virus are evolved? In this study, it was hypothesized that an immunogenic, conserved, short and accessible epitope of the virus with maximum mismatches when aligned with human protein sequences might be a good target for sustainable therapeutics such as antivirals. This hypothesis was based on the premise that antivirals are fabricated to bind strongly and selectively to a target molecule in the form of paratope-epitope complex while skipping all other undesirable bindings. This exquisite affinity and specificity ultimately result in maximizing the antiviral’s precision and minimizing adverse immunological reactions. To achieve this goal, bioinformatic approaches such as BLAST querying and utilizing different NCBI databases were used. In this study, the results were narrowed down to one six-residue sequence, IKWPWY, in the spike protein of SARS-CoV-2, with two mismatches against human protein sequences. Finally, IKWPWY, being a conserved sequence among all strains of human coronavirus, was demonstrated to be likely a reliable and steady target for therapeutics. The conclusion from these findings was that by employing exhaustive bioinformatic algorithms, we might not be too far away from discovering an antiviral that can be used against all strains and variants of human coronavirus provided that the hypothesis of ‘Maximum Mismatch’ is true.