The Peptide A-3302-B Isolated from a Marine Bacterium Micromonospora sp. Inhibits HSV-2 Infection by Preventing the Viral Egress from Host Cells.

Sanya Sureram,Jörn Piel,Somsak Ruchirawat,David Lembo,Manuela Donalisio,Massimo Rittà,Reiko Ueoka,Rachele Francese,Rattanaporn Srivibool,Dhanushka Darshana,Irene Arduino,Prasat Kittakoop,Luisa Muratori

doi:10.3390/ijms23020947

Abstract

Herpesviruses are highly prevalent in the human population, and frequent reactivations occur throughout life. Despite antiviral drugs against herpetic infections, the increasing appearance of drug-resistant viral strains and their adverse effects prompt the research of novel antiherpetic drugs for treating lesions. Peptides obtained from natural sources have recently become of particular interest for antiviral therapy applications. In this work, we investigated the antiviral activity of the peptide A-3302-B, isolated from a marine bacterium, Micromonospora sp., strain MAG 9-7, against herpes simplex virus type 1, type 2, and human cytomegalovirus. Results showed that the peptide exerted a specific inhibitory activity against HSV-2 with an EC50 value of 14 μM. Specific antiviral assays were performed to investigate the mechanism of action of A-3302-B. We demonstrated that the peptide did not affect the expression of viral proteins, but it inhibited the late events of the HSV-2 replicative cycle. In detail, it reduced the cell-to-cell virus spread and the transmission of the extracellular free virus by preventing the egress of HSV-2 progeny from the infected cells. The dual antiviral and previously reported anti-inflammatory activities of A-3302-B, and its effect against an acyclovir-resistant HSV-2 strain are attractive features for developing a therapeutic to reduce the transmission of HSV-2 infections.

Highlights

Herpesviridae is a large family of DNA viruses that includes eight species of pathogenic human viruses
Isolation of the Peptide A-3302-B from the Marine Bacterium Micromonospora sp
-of-addition assayswas were addingthat the early cell membrane–virus interactions were not affected by the peptide

Summary

Introduction

Herpesviridae is a large family of DNA viruses that includes eight species of pathogenic human viruses. Human herpesviruses are ubiquitous, affecting 60–95% of the population worldwide [1,2]. These pathogens can cause a lytic infection with acute clinical manifestations, but a relevant feature of herpesvirus infection is the ability to establish a latent lifelong infection in the host. The latent virus can undergo reactivation determining a recurrent lytic infection in the site of the primary infection or a severe disseminated infection. Human herpesviruses exhibit a spectrum of clinical manifestations, generally self-limiting or asymptomatic. They can cause severe disease in immunocompromised patients, such as those with AIDS or transplant patients. Herpesvirus infections can be transmitted vertically, from the mother to the fetus/newborn, leading to life-threatening illness and long-term sequelae in the infant

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Conclusion