Biology subjects

Bamunuarachchi, G.

Publications and source records attributed to Bamunuarachchi, G..

3 recordsLinked to original sources

bioRxiv2025

Molnupiravir inhibits Bourbon virus infection and disease-associated pathology in mice

Bourbon virus (BRBV) is an emerging tick-borne virus that can cause severe and fatal disease in humans. BRBV is vectored via the Amblyomma americanum tick, which is widely distributed throughout the central, eastern, and southern United States. Serosurveillance studies in Missouri and North Carolina identified BRBV-neutralizing antibodies in approximately 0.6% of tested individuals. To date, no specific antiviral therapy exists. Molnupiravir, an antiviral drug with oral bioavailability, has shown broad-spectrum antiviral activity against RNA viruses, including SARS-CoV-2. Here, we investigated the antiviral activity of molnupiravir against BRBV infection in cell culture and a mouse model of BRBV disease. Molnupiravir suppressed BRBV production in cells. In vivo, pre-exposure administration of molnupiravir protected susceptible type I interferon receptor knockout (Ifnar1-/-) mice against lethal BRBV infection. The protection by molnupiravir was associated with lower virus burden in mouse tissues, improvement of T cell (CD4+, CD8+) and B cell (follicular) profiles in the spleen, improvement of severe thrombocytopenia, and reduced pathology in the spleen and liver of BRBV-infected animals. Finally, therapeutic administration of molnupiravir starting 24 or 48 hours after infection ameliorated weight loss, clinical signs of disease, and lethality associated with BRBV infection. Overall, our experiments suggest that molnupiravir as a potential antiviral therapy for evaluation in humans with BRBV infections.

microbiology↗

bioRxiv2024

Serosurveillance and first detection of Bourbon virus RNA in a wildlife host

Bourbon virus (BRBV) is an emerging pathogen that can cause severe and fatal disease in humans. BRBV is vectored by Amblyomma americanum (lone star ticks), which are widely distributed across the central, southern, and eastern United States. Wildlife species are potentially important for the maintenance and transmission of BRBV, but little is known about which species are involved, and what other factors play a role in the exposure to BRBV. To assess the exposure risk to BRBV among wildlife in the St. Louis area, we collected sera from 98 individuals, representing 6 different mammalian species from two locations in St. Louis County: Tyson Research Center (TRC) and WildCare Park (WCP) from fall 2021 to spring 2023. The sera were used in a BRBV neutralization assay to detect neutralizing antibodies and RT-qPCR for viral RNA analysis. We also sampled and compared the abundance of A. americanum ticks at the two locations and modeled which factors influenced BRBV seropositivity across species. In TRC, we observed a high rate of seropositivity in raccoons (Procyon lotor, 23/25), and white-tailed deer (Odocoileus virginianus, 18/27), but a low rate in opossums (Didelphis virginiana, 1/18). Neutralizing antibodies were also detected in sampled TRC bobcats (Lynx rufus, 4/4), coyotes (Canis latrans, 3/3), and a red fox (Vulpes vulpes, 1/1). The virological analysis identified BRBV RNA in one of the coyote serum samples. In contrast to TRC, all sera screened from WCP were negative for BRBV-specific neutralizing antibodies, and significantly fewer ticks were collected at WCP (31) compared to TRC (2,316). Collectively, these findings suggest that BRBV circulates in multiple wildlife species in the St. Louis area and that tick density and host community composition may be important factors in BRBV ecology.

microbiology↗

bioRxiv2021

mRNA-1273 and Ad26.COV2.S vaccines protect against the B.1.621 variant of SARS-CoV-2

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019, viral variants with greater transmissibility or immune evasion properties have arisen, which could jeopardize recently deployed vaccine and antibody-based countermeasures. Here, we evaluated in mice and hamsters the efficacy of preclinical non-GMP Moderna mRNA vaccine (mRNA-1273) and the Johnson & Johnson recombinant adenoviral-vectored vaccine (Ad26.COV2.S) against the B.1.621 (Mu) South American variant of SARS-CoV-2, which contains spike mutations T95I, Y144S, Y145N, R346K, E484K, N501Y, D614G, P681H, and D950N. Immunization of 129S2 and K18-human ACE2 transgenic mice with mRNA-1273 vaccine protected against weight loss, lung infection, and lung pathology after challenge with B.1.621 or WA1/2020 N501Y/D614G SARS-CoV-2 strain. Similarly, immunization of 129S2 mice and Syrian hamsters with a high dose of Ad26.COV2.S reduced lung infection after B.1.621 virus challenge. Thus, immunity induced by mRNA-1273 or Ad26.COV2.S vaccines can protect against the B.1.621 variant of SARS-CoV-2 in multiple animal models.

microbiology↗