In-Silico Design of a Novel Tridecapeptide Targeting Spike Protein of SARS-CoV-2 Variants of Concern.

Several mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have increased the transmission and mortality rate of coronavirus disease-19 (COVID-19) across the globe. Although many vaccines have been developed, a large proportion of the global population remains at high risk of infection. The current study aims to develop an antiviral peptide capable of inhibiting the interaction of SARS-CoV-2 spike protein and its six major variants with the host cell angiotensin-converting enzyme 2 (ACE2) receptor. An in-silico approach was employed to design a therapeutic peptide inhibitor against the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 and its variants (B.1.1.7, B.1.351, P.1, B.1.617.1, B.1.617.2 and B.1.617.3). The binding specificity and affinity of our designed peptide inhibitor Mod13AApi (YADKYQKQYKDAY) with wild-type S-RBD and its six variants was confirmed by molecular docking using the HPEPDOCK tool, whereas complex stability was determined by the MD simulation study. The physicochemical and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of inhibitory peptides were determined using the ExPASy tool and pkCSM server. The docking results and its properties from our in-silico analysis present the Mod13AApi, a promising peptide for the rapid development of anti-coronavirus peptide-based antiviral therapy. Blockage of the binding of the spike protein of SARS-CoV-2 variants with ACE2 in the presence of the therapeutic peptide may prevent deadly SARS-CoV-2 variants entry into host cells. Therefore, the designed inhibitory peptide can be utilized as a promising therapeutic strategy to combat COVID-19, as evident from this in-silico study.

Exposomes to Exosomes: Exosomes as Tools to Study Epigenetic Adaptive Mechanisms in High-Altitude Humans.

Humans on earth inhabit a wide range of environmental conditions and some environments are more challenging for human survival than others. However, many living beings, including humans, have developed adaptive mechanisms to live in such inhospitable, harsh environments. Among different difficult environments, high-altitude living is especially demanding because of diminished partial pressure of oxygen and resulting chronic hypobaric hypoxia. This results in poor blood oxygenation and reduces aerobic oxidative respiration in the mitochondria, leading to increased reactive oxygen species generation and activation of hypoxia-inducible gene expression. Genetic mechanisms in the adaptation to high altitude is well-studied, but there are only limited studies regarding the role of epigenetic mechanisms. The purpose of this review is to understand the epigenetic mechanisms behind high-altitude adaptive and maladaptive phenotypes. Hypobaric hypoxia is a form of cellular hypoxia, which is similar to the one suffered by critically-ill hypoxemia patients. Thus, understanding the adaptive epigenetic signals operating in in high-altitude adjusted indigenous populations may help in therapeutically modulating signaling pathways in hypoxemia patients by copying the most successful epigenotype. In addition, we have summarized the current information about exosomes in hypoxia research and prospects to use them as diagnostic tools to study the epigenome of high-altitude adapted healthy or maladapted individuals.