The gut–brain axis is a bidirectional communication network connecting the gastrointestinal tract and central nervous system. The axis keeps track of gastrointestinal activities and integrates them to connect gut health to higher cognitive parts of the brain. Disruption in this connection may facilitate various neurological and gastrointestinal problems. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Misfolded protein aggregates that cause cellular toxicity and that aid in the collapse of cellular proteostasis are a defining characteristic of neurodegenerative proteinopathies. These disorders are not only caused by changes in the neural compartment but also due to other factors of non-neural origin. Mounting data reveal that the majority of gastrointestinal (GI) physiologies and mechanics are governed by the central nervous system (CNS). Furthermore, the gut microbiota plays a critical role in the regulation and physiological function of the brain, although the mechanism involved has not yet been fully interpreted. One of the emerging explanations of the start and progression of many neurodegenerative illnesses is dysbiosis of the gut microbial makeup. The present understanding of the literature surrounding the relationship between intestinal dysbiosis and the emergence of certain neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis, is the main emphasis of this review. The potential entry pathway of the pathogen-associated secretions and toxins into the CNS compartment has been explored in this article at the outset of neuropathology. We have also included the possible mechanism of undelaying the synergistic effect of infections, their metabolites, and other interactions based on the current understanding.

SARS-CoV-2 transmissibility is higher than that of other human coronaviruses; therefore, it poses a threat to the populated communities. We investigated mutations among envelope (E), membrane (M), and spike (S) proteins from different isolates of SARS-CoV-2 and plausible signaling influenced by mutated virus in a host. We procured updated protein sequences from the NCBI virus database. Mutations were analyzed in the retrieved sequences of the viral proteins through multiple sequence alignment. Additionally, the data was subjected to ScanPROSITE to analyse if the mutations generated a relevant sequence for host signaling. Unique mutations in E, M, and S proteins resulted in modification sites like PKC phosphorylation and N-myristoylation sites. Based on structural analysis, our study revealed that the D614G mutation in the S protein diminished the interaction with T859 and K854 of adjacent chains. Moreover, the S protein of SARS-CoV-2 consists of an Arg-Gly-Asp (RGD) tripeptide sequence, which could potentially interact with various members of integrin family receptors. RGD sequence in S protein might aid in the initial virus attachment. We speculated crucial host pathways which the mutated isolates of SARS-CoV-2 may alter like PKC, Src, and integrin mediated signaling pathways. PKC signaling is known to influence the caveosome/raft pathway which is critical for virus entry. Additionally, the myristoylated proteins might activate NF-κB, a master molecule of inflammation. Thus the mutations may contribute to the disease pathogenesis and distinct lung pathophysiological changes. Further the frequently occurring mutations in the protein can be studied for possible therapeutic interventions.

Coronaviruses are large positive-sense RNA viruses with spike-like peplomers on their surface. The Coronaviridae family's strains infect different animals and are popularly associated with several outbreaks, namely SARS and MERS epidemic. COVID-19 is one such recent outbreak caused by SARS-CoV-2 identified first in Wuhan, China. COVID-19 was declared a pandemic by WHO on 11th March 2020. Our review provides information covering various facets of the disease starting from its origin, transmission, mutations in the virus to pathophysiological changes in the host upon infection followed by diagnostics and possible therapeutics available to tackle the situation. We have highlighted the zoonotic origin of SARS-CoV-2, known to share 96.2% nucleotide similarity with bat coronavirus. Notably, several mutations in SARS-CoV-2 spike protein, nucleocapsid protein, PLpro, and ORF3a are reported across the globe. These mutations could alter the usual receptor binding function, fusion process with the host cell, virus replication, and the virus's assembly. Therefore, studying these mutations could help understand the virus's virulence properties and design suitable therapeutics. Moreover, the aggravated immune response to COVID-19 can be fatal. Hypertension, diabetes, and cardiovascular diseases are comorbidities substantially associated with SARS-CoV-2 infection. The review article discusses these aspects, stating the importance of various comorbidities in disease outcomes. Furthermore, medications' unavailability compels the clinicians to opt for atypical drugs like remdesivir, chloroquine, etc. The current diagnostics of COVID-19 include qRT-PCR, CT scan, serological tests, etc. We have described these aspects to expose the information to the scientific community and to accelerate the research.