Comparative Bioinformatics Analyses of SARS-CoV-2 Spike Glycoproteins in Different Countries

In this study, 27 protein sequences of SARS-CoV-2 spike (S) glycoprotein from 23 different countries were analyzed using bioinformatics approaches. In this context, post-translational modifications, sequence and domain analyses, phylogenetic analysis, and 3D structure analysis of the spike glycoprotein proteins were performed. Also, molecular docking analysis of the SARS-CoV-2 spike protein S1 receptor-binding domain (SS1) with human ACE2 protein was conducted. It was found that although all SARS-CoV-2s include Spike_rec_bind (PF09408) and Corona_S2 (PF01601) domain structures, the Cterminal S2 region was more diverse than the S1 region. The predicted N-glycosylation and phosphorylation sites were determined to be between 17 and 19 and 136 and 168, respectively. In phylogenetic analysis, SARS-CoV-2s were found to have more similarity with bat RaTG13 and pangolin CoV-2 than MERS CoV and bat SARS CoV. The predicted 3D protein structures of human SARS-CoV-2 and bat RaTG13 showed high similarity, ranging from 0.76 to 0.78. The docking analyses revealed that Asp30, Lys31, His34, Glu35, Glu37, Asp38, Asn330, and Gln325 residues were binding residues in the ACE2 protein for the Nterminal S1 subunit of SARS-CoV-2. The findings are particularly important for the studies of drug development and drug design. © 2022, ABADER (Adıyaman Bilimsel Arastırmalar Dernegi). All rights reserved.

Can ACE2 Receptor Polymorphism Predict Species Susceptibility to SARS-CoV-2?

A novel severe acute respiratory syndrome coronavirus, SARS-CoV-2, emerged in China in December 2019 and spread worldwide, causing more than 1.3 million deaths in 11 months. Similar to the human SARS-CoV, SARS-CoV-2 shares strong sequence homologies with a sarbecovirus circulating in Rhinolophus affinis bats. Because bats are expected to be able to transmit their coronaviruses to intermediate animal hosts that in turn are a source of viruses able to cross species barriers and infect humans (so-called spillover model), the identification of an intermediate animal reservoir was the subject of intense researches. It was claimed that a reptile (Ophiophagus hannah) was the intermediate host. This hypothesis was quickly ruled out and replaced by the pangolin (Manis javanica) hypothesis. Yet, pangolin was also recently exonerated from SARS-CoV-2 transmission to humans, leaving other animal species as presumed guilty. Guided by the spillover model, several laboratories investigated in silico the species polymorphism of the angiotensin I converting enzyme 2 (ACE2) to find the best fits with the SARS-CoV-2 spike receptor-binding site. Following the same strategy, we used multi-sequence alignment, 3-D structure analysis, and electrostatic potential surface generation of ACE2 variants to predict their binding capacity to SARS-CoV-2. We report evidence that such simple in silico investigation is a powerful tool to quickly screen which species are potentially susceptible to SARS-CoV-2. However, possible receptor binding does not necessarily lead to successful replication in host. Therefore, we also discuss here the limitations of these in silico approaches in our quest on the origins of COVID-19 pandemic.

The COVID-19 puzzle: a global nightmare.

In December 2019, WHO was informed with several unknown pneumonia cases and later it was found as highly contagious, transmittable and pathogenic viral infection. The novel coronavirus (nCoV-19) was firstly reported from Wuhan city in China. COVID-19 has raised the concern of the world since its emergence from China. The WHO has declared an ongoing COVID-19 outbreak as a pandemic. Till now 6,057,853 confirmed cases with 371,166 deaths have been reported from approximately 213 countries of the world. The aim of this study is to discuss all the aspects related to recently discovered novel coronavirus. The article, therefore, provides a comprehensive study on the genomic, epidemiological, social, clinical and environmental aspects of SARS-CoV-2. SARS-CoV-2 uses human ACE2 receptor as a ligand to bind and transmit its genome just like the SARS-CoV. The clinical symptoms of SARS-CoV-2 are very non-specific and include fever, sore throat, wheezing, rales, headache and rhinorrhoea with round-glass pulmonary opacifications shadowing in X-ray. Many antiviral drugs show efficacy but only in mild to moderate infection levels. Though efforts on development of SARS-CoV-2 vaccine have been started earlier as soon as the pandemic was emerged, till date no effective drug or vaccine has been validated with significant efficacy against the disease; therefore, there is a dire need to design effective vaccine against SARS-CoV-2. Multiple vaccine candidates are still in evaluation and exploratory stages on different clinical models with potential results on different animals and human models. mRNA-1273, ChAdOx1, Ad5-nCoV, INO-4800, LV-SMENP-DC and pathogen-specific aAPC are the most advanced and potential drug candidates against COVID-19. Recent studies have revealed any attractive vaccine candidates as promising therapeutic agents based on different strategies of vaccines. Here, the rationale of this review was also to provide an overview of the pathogenesis of the virus and summarize the updated potential vaccine candidates against SARS-CoV-2.