COVID-19 Challenge: A Quest for Effective Vaccine Strategies Against Circulating and Emerging SARS-CoV-2 Variants.

INTRODUCTION: SARS-CoV-2 belongs to the coronavirus family, a large family of viruses infecting avian and mammalian hosts. Accumulated mutations over time in the genome of SARS-CoV-2 have given rise to different variants differing in type and sequence. Variants that did not affect transmissibility, infectivity, and severity have gone unnoticed, and mutations that made the virus unfit for survival were eventually deleted from the gene pool. An emerging variant in the host population needs to be monitored closely for its infection consequences. In addition, the variants of concern (VOC) need to be focused on developing effective disease-fighting regimes. As viral epidemics are better fought using effective vaccines, several vaccines have been developed and used since December 2020. The central point of the present study is the continuous variation in the genome of SARS-CoV-2, instigating the researchers to refine their modus operandi to fight against COVID-19. METHODS: Prominent medical and literature databases were searched using relevant keywords to gather study results, reports, and other data helpful in writing this narrative review. RESULTS: This article successfully collates information about the structure and life cycle of SARS-CoV-2, followed by types and nomenclature of mutations in SARS-CoV-2. Variants B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron) are current VOCs due to their widespread transmission capability and probable immune evasion. Furthermore, this review article presents information about the major vaccines available and those under development. Based on the original and new strains of SARS-CoV-2, 19 vaccines have been granted emergency use or conditional marketing approvals, 141 are under clinical development, and 194 are in preclinical development stages worldwide. CONCLUSION: Continuous variation in the genome of SARS-CoV-2, presenting new VOCs frequently, has posed a compelling need to amend and evolve current and future vaccine development strategies to overpower the ever-evolving virus.

A new class of half-sandwich ruthenium complexes containing Biginelli hybrids: anticancer and anti-SARS-CoV-2 activities.

In order to discover new dual-active agents, a series of novel Biginelli hybrids (tetrahydropyrimidines) and their ruthenium(II) complexes were synthesized. Newly synthesized compounds were characterized by IR, NMR, and X-ray techniques and investigated for their cytotoxic effect on human cancer cell lines HeLa, LS174, A549, A375, K562 and normal fibroblasts (MRC-5). For further examination of the cytotoxic mechanisms of novel complexes, two of them were chosen for analyzing their effects on the distribution of HeLa cells in the cell cycle phases. The results of the flow cytometry analysis suggest that the proportion of cells in G2/M phase was decreased following the increase of subG1 phase in all treatments. These results confirmed that cells treated with 5b and 5c were induced to undergo apoptotic death. The ruthenium complexes 5a-5d show significant inhibitory potency against SARS-CoV-2 Mpro. Therefore, molecule 5b has significance, while 5e possesses the lowest values of ΔGbind and Ki, which are comparable to cinanserin, and hydroxychloroquine. In addition, achieved results will open a new avenue in drug design for more research on the possible therapeutic applications of dual-active Biginelli-based drugs (anticancer-antiviral). Dual-active drugs based on the hybridization concept "one drug curing two diseases" could be a successful tactic in healing patients who have cancer and the virus SARS-CoV-2 at the same time.