How Concerning Is a Sars-Cov-2 Variant of Concern? Computational Predictions and the Variants Labeling System

Abstract

We herein report a study to evaluate the use of computational prediction of SARS-CoV-2 genetic variations in improving the current variants labeling system. First, we reviewed the basis of the system developed by the World Health Organization (WHO) for the labeling of SARS-CoV-2 genetic variants and the adaptations made to it by the United States Center of Diseases Control (CDC). We observed that the labeling system is based upon the virus major attributes. However, we found that the labeling criteria of the SARS-CoV-2 variants derived from these attributes are not accurately defined and are used differently by the two health management agencies. Consequently, discrepancies exist between the labels given by WHO and CDC to same variants. Our observations suggest that giving the VOC label to a new variant is premature and might not be appropriate. Therefore, we carried out a comparative computational study to predict the effects of the mutations on the virus structure and functions of five VOCs. By linking these data to the criteria used by WHO and the CDC for variant labeling, we ascertained that comparative computational predictions of the impact of genetic variations are a better ground for rapid and more accurate labelling of SARS-CoV-2 variants. We propose to label all emergent variants VUM or VBM and to carry out computational predictive studies and thorough variants comparison, upon which more appropriate and informative labels can be attributed. Furthermore, harmonization of the variants labeling system would be globally beneficial to communicate about and fight COVID19 pandemic.

In silico evaluation of ten monoclonal antibodies neutralization power of SARS-CoV-2 variants EG.5 and BA.2.86

“…In conclusion, our previously described In silico method [15] to evaluate available SARS-CoV-2 antibodies neutralizing power with the new emerging variants EG.5 and BA.2.86 showed to be reliable and effective for preliminary evaluation of new neutralizing antibodies and their cocktails. This paper supports our described method, and it is the first paper to discuss the neutralizing efficiency of all available emergency authorized neutralizing antibodies with the new SARS-CoVvariants.…”

“…SARS-CoV-2 variants-specific mutations were introduced to the collected sequence to generate the different variant sequences based on published mutations in the Stanford University SARS-CoV-2 Variants database (https://covdb.stanford.edu/variants/omicron_ba_1_3/) [17]. The spikes 3D monomeric structures were modeled in an open state form as described in our previous report [15]. using the SWISS-MODEL server -User Template Mode [18] (https://swissmodel.expasy.org/interactive#structure) and Omicron's template model.…”

“…Each of the examined NAbs showed to have different binding site on the RBD domain. Moreover, as previously described [15], NAbs are categorized based on binding to a specific RBD epitope or based on whether it is competing with the angiotensin-converting enzyme 2 (ACE2). The selected NAbs were from class I, II and III as shown in Figure 1.…”

“…In the work we are reporting herein, we applied the computational method we previously described to evaluate SARS-CoV-2 antibodies neutralization power [15], to assess the effectiveness of the available SARS-CoV-2 neutralizing antibodies on the newly emerged variants Eris and Pirola. We modeled nine different neutralizing antibodies previously approved by FDA and EMA for the treatment of mild to moderate COVID-19 symptoms and measured their binding affinities to the new variants in comparison to the original Wuhan strain for which they were granted emergency authorizationuse.…”