Deciphering HIV-1 Resistance Pathways against Capsid Inhibitors in vitro and in Humanized Mice
NIAID - National Institute of Allergy and Infectious Diseases
About This Grant
PROJECT SUMMARY The HIV-1 capsid, a cone-shaped protein shell, is a promising target for antiviral interventions, with lenacapavir (LEN), a potent capsid inhibitor, demonstrating efficacy in treatment and prevention. However, resistance to LEN has been reported in both in vitro and clinical contexts. Our preliminary studies have also identified LEN-resistant mutations not previously observed. As the use of capsid inhibitors is expected to expand in the future, a deeper understanding of drug resistance—especially its evolutionary trajectories and impact on viral fitness and transmissibility—is crucial, with broad clinical implications. In this grant, we will investigate HIV-1 resistance to LEN, exploring its potential and consequences using in vitro and in vivo models. In Aim 1, we will elucidate how HIV-1 acquires increased resistance to LEN through rationally designed, accelerated in vitro evolution approaches. We will use large-scale mutant libraries combined with multiplex selection and viral adaptation to comprehensively map drug resistance pathways. These LEN- resistant variants will then be assessed in a humanized mouse model of HIV-1 LEN treatment. LEN is under investigation for pre-exposure prophylaxis; however, the transmissibility of LEN-resistant HIV-1 variants remains unclear and may impact future prevention efforts. To address this, we will evaluate the transmission efficiency of LEN-resistant variants in a humanized mouse model of mucosal transmission. CA mutations conferring LEN resistance can affect multiple CA-dependent functions, potentially influencing viral transmissibility. Correlates of transmission by LEN-resistant variants will be determined using both high- throughput phenotypic assays and in vivo experiments.
Grant Summary
Deciphering HIV-1 Resistance Pathways against Capsid Inhibitors in vitro and in Humanized Mice is a NIAID - National Institute of Allergy and Infectious Diseases grant providing up to $791K for university, nonprofit, healthcare org. Applications are due 2031-01-31 (open). Check eligibility and apply with FindGrants.
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Up to $791K
2031-01-31
- 1Confirm your organization is eligible for Deciphering HIV-1 Resistance Pathways against Capsid Inhibitors in vitro and in Humanized Mice from NIAID - National Institute of Allergy and Infectious Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
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Deciphering HIV-1 Resistance Pathways against Capsid Inhibitors in vitro and in Humanized Mice: Frequently Asked Questions
Who is eligible for the Deciphering HIV-1 Resistance Pathways against Capsid Inhibitors in vitro and in Humanized Mice?
Deciphering HIV-1 Resistance Pathways against Capsid Inhibitors in vitro and in Humanized Mice is offered by NIAID - National Institute of Allergy and Infectious Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Deciphering HIV-1 Resistance Pathways against Capsid Inhibitors in vitro and in Humanized Mice provide?
Deciphering HIV-1 Resistance Pathways against Capsid Inhibitors in vitro and in Humanized Mice provides up to $791K per award from NIAID - National Institute of Allergy and Infectious Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Deciphering HIV-1 Resistance Pathways against Capsid Inhibitors in vitro and in Humanized Mice deadline?
Applications for Deciphering HIV-1 Resistance Pathways against Capsid Inhibitors in vitro and in Humanized Mice are due 2031-01-31 (open). Because deadlines can change, verify the date with the funder, NIAID - National Institute of Allergy and Infectious Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Deciphering HIV-1 Resistance Pathways against Capsid Inhibitors in vitro and in Humanized Mice?
To apply for Deciphering HIV-1 Resistance Pathways against Capsid Inhibitors in vitro and in Humanized Mice, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIAID - National Institute of Allergy and Infectious Diseases.