Immune escape facilitation by mutations of epitope residues in RdRp of SARS-CoV-2.

Mutations drive viral evolution and genome variability that causes viruses to escape host immunity and to develop drug resistance. SARS-CoV-2 has considerably higher mutation rate. SARS-CoV-2 possesses a RNA dependent RNA polymerase (RdRp) which helps to replicate its genome. The mutation P323L in RdRp is associated with the loss of a particular epitope (321-327) from this protein. We consider the effects of mutations in some of the epitope region including the naturally occurring mutation P323L on the structure of the epitope and their interface with paratope using all-atom molecular dynamics (MD) simulation studies. We observe that the mutations cause conformational changes in the epitope region by opening up the region associated with increase in the radius of gyration and intramolecular hydrogen bonds, making the region less accessible. Moreover, we study the conformational stability of the epitope region and epitope:paratope interface under the mutation from the fluctuations in the dihedral angles. We observe that the mutation renders the epitope and the epitope:paratope interface unstable compared to the corresponding wild type ones. Thus, the mutations may help in escaping antibody mediated immunity of the hostCommunicated by Ramaswamy H. Sarma.

Surge of mucormycosis during the COVID-19 pandemic.

Patients with respiratory viral infections are more likely to develop co-infections leading to increased fatality. Mucormycosis is an epidemic amidst the COVID-19 pandemic that conveys a 'double threat' to the global health fraternity. Mucormycosis is caused by the Mucorales group of fungi and exhibits acute angioinvasion generally in immunocompromised patients. The most familiar foci of infections are sinuses (39%), lungs (24%), and skin tissues (19%) where the overall dissemination occurs in 23% of cases. The mortality rate in the case of disseminated mucormycosis is found to be 96%. Symptoms are mostly nonspecific and often resemble other common bacterial or fungal infections. Currently, COVID-19-associated mucormycosis (CAM) is being reported from a number of countries such as the USA, Turkey, France, Mexico, Iran, Austria, UK, Brazil, and Italy, while India is the hotspot for this deadly co-infection, accounting for approximately 28,252 cases up to June 8, 2021. It strikes patients within 12-18 days after COVID-19 recovery, and nearly 80% require surgery. Nevertheless, the mortality rate can reach 94% if the diagnosis is delayed or remains untreated. Sometimes COVID-19 is the sole predisposing factor for CAM. Therefore, this study may provide a comprehensive resource for clinicians and researchers dealing with fungal infections, intending to link the potential translational knowledge and prospective therapeutic challenges to counter this opportunistic pathogen.

A natural food preservative peptide nisin can interact with the SARS-CoV-2 spike protein receptor human ACE2.

Nisin, a food-grade antimicrobial peptide produced by lactic acid bacteria has been examined for its probable interaction with the human ACE2 (hACE2) receptor, the site where spike protein of SARS-CoV-2 binds. Among the eight nisin variants examined, nisin H, nisin Z, nisin U and nisin A showed a significant binding affinity towards hACE2, higher than that of the RBD (receptor binding domain) of the SARS-CoV-2 spike protein. The molecular interaction of nisin with hACE2 was investigated by homology modeling and docking studies. Further, binding efficiency of the most potent nisin H was evaluated through the interaction of hACE2:nisin H complex with RBD (receptor-binding domain) of SARS-CoV-2 and that of hACE2:RBD complex with nisin H. Here, nisin H acted as a potential competitor of RBD to access the hACE2 receptor. The study unravels for the first time that a globally used food preservative, nisin has the potential to bind to hACE2.

Non-synonymous mutations of SARS-CoV-2 leads epitope loss and segregates its variants.

The non-synonymous mutations of SARS-CoV-2 isolated from across the world have been identified during the last few months. The surface glycoprotein spike of SARS-CoV-2 forms the most important hotspot for amino acid alterations followed by the ORF1a/ORF1ab poly-proteins. It is evident that the D614G mutation in spike glycoprotein and P4715L in RdRp is the important determinant of SARS-CoV-2 evolution since its emergence. P4715L in RdRp, G251V in ORF3a and S1498F of Nsp3 is associated with the epitope loss that may influence pathogenesis caused by antibody escape variants. The phylogenomics distinguished the ancestral viral samples from China and most part of Asia, isolated since the initial outbreak and the later evolved variants isolated from Europe and Americas. The evolved variants have been found to predominant globally with the loss of epitopes from its proteins. These have implications for SARS-CoV-2 transmission, pathogenesis and immune interventions.