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The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its new variants reported in different countries have posed a serious threat to human health and social fabrics worldwide. In addition, these new variants hindered the efforts of vaccines and other therapeutic developments. In this review article, we explained the emergence of new variants of SARS-CoV-2, their transmission risk, mortality rate, and, more importantly, the impact of each new variant on the efficacy of the developed vaccines reported in different literature and findings. The literature reported that with the emergence of new variants, the efficacy of different vaccines is declined, hospitalization is increased while the risk of reinfection also increased. The reports concluded that the emergence of a variant that entirely evades the immune response triggered by the vaccine is improbable. The emergence of new variants and reports of re-infections are creating a more distressing situation and therefore demands further investigation to formulate an effective therapeutic strategy.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Reports of new variants that potentially increase virulence and viral transmission, as well as reduce the efficacy of available vaccines, have recently emerged. In this study, we computationally analyzed the N439K, S477 N, and T478K variants for their ability to bind Angiotensin-converting enzyme 2 (ACE2). We used the protein-protein docking approach to explore whether the three variants displayed a higher binding affinity to the ACE2 receptor than the wild type. We found that these variants alter the hydrogen bonding network and the cluster of interactions. Additional salt bridges, hydrogen bonds, and a high number of non-bonded contacts (i.e., non-bonded interactions between atoms in the same molecule and those in other molecules) were observed only in the mutant complexes, allowing efficient binding to the ACE2 receptor. Furthermore, we used a 2.0-μs all-atoms simulation approach to detect differences in the structural dynamic features of the resulting protein complexes. Our findings revealed that the mutant complexes possessed stable dynamics, consistent with the global trend of mutations yielding variants with improved stability and enhanced affinity. Binding energy calculations based on molecular mechanics/generalized Born surface area (MM/GBSA) further revealed that electrostatic interactions principally increased net binding energies. The stability and binding energies of N439K, S477 N, and T478K variants were enhanced compared to the wild-type-ACE2 complex. The net binding energy of the systems was −31.86 kcal/mol for the wild-type-ACE2 complex, −67.85 kcal/mol for N439K, −69.82 kcal/mol for S477 N, and −69.64 kcal/mol for T478K. The current study provides a basis for exploring the enhanced binding abilities and structural features of SARS-CoV-2 variants to design novel therapeutics against the virus.

Background: GLI2, a zinc finger transcription factor, mediates Sonic hedgehog signaling, a critical pathway in vertebrate embryogenesis. GLI2 has been implicated in diverse set of embryonic developmental processes, including patterning of central nervous system and limbs. In humans, mutations in GLI2 are associated with several developmental defects, including holoprosencephaly and polydactyly. Results: Here, we demonstrate in transient transgenic zebrafish assays, the potential of a subset of tetrapod-teleost conserved non-coding elements (CNEs) residing within human GLI2 intronic intervals to induce reporter gene expression at known regions of endogenous GLI2 transcription. The regulatory activities of these elements are observed in several embryonic domains, including neural tube and pectoral fin. Moreover, our data reveal an overlapping expression profile of duplicated copies of an enhancer during zebrafish evolution. Conclusions: Our data suggest that during vertebrate history GLI2 acquired a high level of complexity in the genetic mechanisms regulating its expression during spatiotemporal patterning of the central nervous system (CNS) and limbs. Developmental Dynamics 244:681-692, 2015. V C 2015 Wiley Periodicals, Inc.