Researchers Discover Molecular Switch Blocking Herpes Virus Entry
Researchers have identified a critical molecular switch in herpes viruses that enables cellular invasion, offering a potential target for new antiviral therapies. The team used artificial intelligence, molecular simulations, and laboratory experiments to pinpoint a single amino acid residue essential for the virus’s fusion machinery. Altering this residue prevented the virus from entering host cells in tests. This finding applies to multiple herpesviruses, including those causing cold sores, genital herpes, and chickenpox.
The switch involves a specific conformation in the viral glycoprotein complex responsible for membrane fusion. Computational modeling predicted the key amino acid, which experiments confirmed by mutating it and observing complete inhibition of entry. Herpes simplex virus type 1 and type 2, along with varicella-zoster virus, rely on this mechanism. The discovery reveals a conserved vulnerability across the herpesvirus family.
Herpesviruses infect billions worldwide, establishing lifelong latency and causing recurrent outbreaks. Current treatments like acyclovir target viral replication but do not prevent initial infection or eliminate latent virus. Blocking entry at the fusion stage could provide prophylactic options or complement existing drugs. The approach avoids resistance issues common with replication inhibitors.
The study combined AlphaFold predictions with dynamic simulations to screen fusion proteins rapidly. Researchers tested candidates in cell cultures, finding one mutation that locked the glycoprotein in a pre-fusion state. This prevented the structural changes needed for viral envelope merger with cell membranes. Results held across different cell types, indicating broad efficacy.
Development of entry inhibitors has lagged due to the complexity of herpes fusion proteins. Previous attempts targeted downstream steps, yielding limited success. This precise atomic-level insight accelerates drug design, potentially leading to small molecules or antibodies mimicking the blocking effect. The method demonstrates AI’s role in accelerating virology research.
Herpesviruses contribute to significant health burdens, including neonatal infections and complications in immunocompromised patients. Epstein-Barr virus and cytomegalovirus, also herpes family members, cause cancers and transplant issues. A universal entry blocker could address multiple pathogens simultaneously. Researchers plan to optimize compounds for in vivo testing.
The breakthrough highlights interdisciplinary approaches in infectious disease research. Machine learning reduced screening time from years to months by prioritizing targets. Experimental validation used pseudovirus systems for safe handling of dangerous pathogens. Funding supported collaborative efforts across institutions focused on structural virology.
Ongoing work aims to crystallize the mutated complex for higher-resolution structures. Partners seek to develop topical or systemic inhibitors for clinical trials. The discovery adds to growing tools against persistent viral threats. It underscores the value of basic research in uncovering exploitable weaknesses in pathogens.
This advance occurs amid rising interest in broad-spectrum antivirals. Similar strategies target influenza and coronaviruses through conserved entry mechanisms. The herpes finding provides a blueprint for tackling other enveloped viruses. Future therapies may prevent transmission and reactivation more effectively than current options.
