Biology subjects

Panchal, R.

Publications and source records attributed to Panchal, R..

2 recordsLinked to original sources

bioRxiv2025

Dose response comparison of Nipah virus strains Malaysia and Bangladesh in hamsters exposed by the intranasal or intraperitoneal route

Nipah virus, a zoonotic pathogen, can cause debilitating disease and death in humans. Currently, countermeasures are limited, with several in various stages of testing but none yet FDA-approved for human use. Evaluation of countermeasure candidates requires safety testing in humans, as well as efficacy testing against lethal challenge in animal models. Herein, we describe the characterization and comparison of the intraperitoneal and intranasal Syrian golden hamster models for Nipah virus strains Malaysia and Bangladesh. Overall, the intraperitoneal route of exposure resulted in a more consistent lethal outcome, regardless of virus strain. Therefore, the IP model was subsequently used to evaluate the use of Favipiravir as a potential positive control for future studies investigating NiV countermeasures. In contrast to prior reported results regarding Favipiravir in Nipah virus-infected hamsters, Favipiravir was only fifty percent effective at preventing death following lethal challenge, regardless of Nipah virus strain. The data suggest that Favipiravir is only partially protective against Nipah virus in hamsters, and, thus, would likely not be an ideal candidate as a positive control in future efficacy studies.

microbiology↗

bioRxiv2024

The landscape of regional missense mutational intolerance quantified from 125,748 exomes

Missense variants can have a range of functional impacts depending on factors such as the specific amino acid substitution and location within the gene. To interpret their deleteriousness, studies have sought to identify regions within genes that are specifically intolerant of missense variation. Here, we leverage the patterns of rare missense variation in 730,947 exome sequenced individuals in the Genome Aggregation Database (gnomAD v4.1.1) against a null mutational model to identify transcripts with regional differences in missense constraint. Missense-depleted regions are enriched for ClinVar pathogenic variants, de novo missense variants from individuals with neurodevelopmental disorders, and complex trait heritability. Following ClinGen calibration recommendations for the ACMG/AMP variant classification guidelines, we establish that variants within regions with <36% of their expected missense variation achieve moderate support for pathogenicity. We integrate this regional constraint measure into a missense deleteriousness metric (named MPC) that effectively stratifies rare and de novo missense variants in individuals with early-onset developmental conditions from controls. These results provide additional tools to aid in missense variant interpretation.

genomics↗