Neutralizing antibodies to block viral entry and for identification of entry inhibitors

Neutralizing antibodies (NAbs) are naturally produced by our immune system to combat viral infections. Clinically, neutralizing antibodies with potent efficacy and high specificity have been extensively used to prevent and treat a wide variety of viral infections, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Human Immunodeficiency Virus (HIV), Dengue Virus (DENV) and Hepatitis B Virus (HBV). An overwhelmingly large subset of clinically effective NAbs operates by targeting viral envelope proteins to inhibit viral entry into the host cell. Binding of viral envelope protein to the host receptor is a critical rate limiting step triggering a cascade of downstream events, including endocytosis, membrane fusion and pore formation to allow viral entry. In recent years, improved structural knowledge on these processes have allowed researchers to also leverage NAbs as an indispensable tool in guiding discovery of novel antiviral entry inhibitors, providing drug candidates with high efficacy and pan-genus specificity. This review will summarize the latest progresses on the applications of NAbs as effective entry inhibitors and as important tools to develop antiviral therapeutics by high-throughput drug screenings, rational design of peptidic entry inhibitor mimicking NAbs and in silico computational modeling approaches.