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Fusion inhibitors that block host-to-host transmission of SARS-CoV-2

阻止 SARS-CoV-2 宿主间传播的融合抑制剂

基本信息

批准号：
10237600
负责人：
Matteo Porotto
金额：
$ 75.02万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10237600
关键词：
2019-nCoV Address Affinity Animals Antiviral Agents Binding Biodistribution Biological Assay COVID-19 COVID-19 pandemic COVID-19 treatment Cell Culture Techniques Cell fusion Cell membrane Cell surface Cells Chiroptera Common Cold Communities Coronavirus Coronavirus Infections Couples Data Development Disease Disease Outbreaks Distal Dominant-Negative Mutation Dose Endosomes Ferrets Glycoproteins Homes for the Aged Hospitals Human Immunologics In Vitro Individual Infection Infection prevention Integration Host Factors Lead Life Lipids Mediating Membrane Membrane Fusion Middle East Respiratory Syndrome Coronavirus Modeling Molecular Molecular Conformation Names Nose Peptide Hydrolases Peptides Play Population Process Prophylactic treatment Proteins Role SARS coronavirus Severe Acute Respiratory Syndrome Severity of illness Surface Testing Therapeutic Intervention Toxic effect Vaccinated Vaccines Viral Virus Virus Diseases World Health Organization Zoonoses base betacoronavirus cell type cytotoxicity design dimer experimental study fundamental research genetic information improved in vivo inhibitor/antagonist monomer novel novel coronavirus pandemic disease pre-clinical preclinical study pressure prevent receptor receptor binding research clinical testing transmission process uptake viral transmission virus genetics

项目摘要

Coronaviruses (CoVs) can cause life-threatening diseases. The recently emerging coronavirus-related illness was named coronavirus disease 2019 (abbreviated “COVID-19”) by the World Health Organization. COVID-19 is caused by SARS-CoV-2. Like its predecessors SARS-CoV and MERS-CoV, SARS-CoV-2 (S-CoV-2) is a betacoronavirus that is thought to have originated in bats. Originally its spread was animal-to-human, but human-to-human transmission is now widespread. No vaccines and treatments for COVID-19 are available, and these are urgently needed to address the outbreak as well as inevitable ongoing infection. Antivirals that target viral entry into the host cell have been proven effective against a wide range of viruses. In this proposal, we will apply the results of our fundamental research to the development of novel peptide inhibitors of SARS- CoV-2 entry. We have designed lipid-conjugated fusion-inhibitory peptides that efficiently inhibit coronavirus infection in in vitro, ex vivo, and in vivo. We propose to synthesize and evaluate novel lipidated peptides that have enhanced efficacy. These inhibitors will be evaluated for antiviral activity against live SARS-CoV-2 virus. Promising candidates will be tested in transmission experiments in a ferret model. This application will determine whether our approach to entry inhibition of SARS-CoV-2 prevents infection in vivo. 1. To optimize antiviral potency of HRC-lipopeptide fusion inhibitors. 2. To pre-clinically evaluate HRC-lipopeptide fusion inhibitors biodistribution, toxicity and protection against SARS-CoV-2 infection or transmission in vivo.

冠状病毒可导致危及生命的疾病。最近新出现的冠状病毒相关疾病