Considering epitopes conservity in targeting SARS-CoV-2 mutations in variants: a novel immunoinformatics approach to vaccine design.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has gained mutations at an alarming rate in the past years. Developing mutations can increase the virus's pathogenicity and virulence; reduce the efficacy of vaccines, antibodies neutralization, and even challenge adaptive immunity. So, it is essential to identify conserved epitopes (with fewer mutations) in different variants with appropriate antigenicity to target the variants by an appropriate vaccine design. Yet as, 3369 SARS-CoV-2 genomes were collected from global initiative on sharing avian flu data. Then, mutations in the immunodominant regions (IDRs), immune epitope database (IEDB) epitopes, and also predicted epitopes were calculated. In the following, epitopes conservity score against the total number of events (mutations) and the number of mutated sites in each epitope was weighted by Shannon entropy and then calculated by the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS). Based on the TOPSIS conservity score and antigenicity score, the epitopes were plotted. The result demonstrates that almost all epitopes and IDRs with various lengths have gained different numbers of mutations in dissimilar sites. Herein, our two-step calculation for conservity recommends only 8 IDRs, 14 IEDB epitopes, and 10 predicted epitopes among all epitopes. The selected ones have higher conservity and higher immunogenicity. This method is an open-source multi-criteria decision-making platform, which provides a scientific approach to selecting epitopes with appropriate conservity and immunogenicity; against ever-changing viruses.

Antibacterial, antibiofilm, anti-inflammatory, and wound healing effects of nanoscale multifunctional cationic alternating copolymers.

Infectious diseases caused by new or unknown bacteria and viruses, such as anthrax, cholera, tuberculosis and even COVID-19, are a major threat to humanity. Thus, the development of new synthetic compounds with efficient antimicrobial activity is a necessity. Herein, rationally designed novel multifunctional cationic alternating copolymers were directly synthesized through a step-growth polymerization reaction using a bivalent electrophilic cross-linker containing disulfide bonds and a diamine heterocyclic ring. To optimize the activity of these alternating copolymers, several different diamines and cross-linkers were explored to find the highest antibacterial effects. The synthesized nanopolymers not only displayed good to excellent antibacterial activity as judged by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Escherichia coli, but also reduced the number of biofilm cells even at low concentrations, without killing mammalian cells. Furthermore, in vivo experiments using infected burn wounds in mice demonstrated good antibacterial activity and stimulated wound healing, without causing systemic inflammation. These findings suggest that the multifunctional cationic nanopolymers have potential as a novel antibacterial agent for eradication of multidrug resistant bacterial infections.