TY - JOUR

T1 - Antiviral properties of verdazyls and leucoverdazyls and their activity against group B enteroviruses

AU - Volobueva, Aleksandrina S.

AU - Zarubaev, Vladimir V.

AU - Fedorchenko, Tatyana G.

AU - Lipunova, Galina N.

AU - Tungusov, Vladislav N.

AU - Chupakhin, Oleg N.

N1 - The St. Petersburg Pasteur Institute.

PY - 2023

Y1 - 2023

N2 - Enteroviruses are non-enveloped viruses of Enterovirus genus, Picornaviridae family, causing a variety of human diseases: from acute respiratory and intestinal infections to more severe pathologies including poliomyelitis, encephalitis, myocarditis, pancreatitis. Currently, no approved direct-acting antiviral drugs for treatment of enterovirus infections exists, whereas vaccination is available only for prevention of poliomyelitis and enterovirus 71 infection. Therefore, it is promising to conduct a search for inhibitors of enteroviruses life cycle in drug development to treat enterovirus infections. Here, antiviral properties of stable free radicals, verdazyls, and their precursors, leucoverdazyls, were investigated. It has been shown that leucoverdazyls vs verdazyls increased the survival of permissive cell culture infected with coxsackievirus. The activity range of the lead leucoverdazyl against RNA-containing and DNA-containing human viruses (in the viral yield reduction assay) and its proposed mechanism of action (time of addition assay) was studied. The lead compound suppressed reproduction of group B enteroviruses in vitro, with modest activity against influenza A virus and no activity against herpes virus type 1 and adenovirus type 5. The maximum decrease in viral titers was observed upon its addition to infected cells during early and middle stages of the virus life cycle. Thus, we concluded that the studied compound has a pronounced inhibitory activity against group B enteroviruses not belonging to the class of capsid binder inhibitors, without virucidal properties. Previously, we described antioxidant properties of leucoverdazyls. It is known that many viral infections are accompanied by production of reactive oxygen species and oxidative stress, and some compounds with antioxidant properties exhibit antiviral potential. Targeted chemical modifications of leucoverdazyls and further studies of leucoverdazyl mechanism of action as well as in vivo animal studies are needed. However, the results obtained may be useful for future development of new antiviral drugs to treat enteroviral infections.

AB - Enteroviruses are non-enveloped viruses of Enterovirus genus, Picornaviridae family, causing a variety of human diseases: from acute respiratory and intestinal infections to more severe pathologies including poliomyelitis, encephalitis, myocarditis, pancreatitis. Currently, no approved direct-acting antiviral drugs for treatment of enterovirus infections exists, whereas vaccination is available only for prevention of poliomyelitis and enterovirus 71 infection. Therefore, it is promising to conduct a search for inhibitors of enteroviruses life cycle in drug development to treat enterovirus infections. Here, antiviral properties of stable free radicals, verdazyls, and their precursors, leucoverdazyls, were investigated. It has been shown that leucoverdazyls vs verdazyls increased the survival of permissive cell culture infected with coxsackievirus. The activity range of the lead leucoverdazyl against RNA-containing and DNA-containing human viruses (in the viral yield reduction assay) and its proposed mechanism of action (time of addition assay) was studied. The lead compound suppressed reproduction of group B enteroviruses in vitro, with modest activity against influenza A virus and no activity against herpes virus type 1 and adenovirus type 5. The maximum decrease in viral titers was observed upon its addition to infected cells during early and middle stages of the virus life cycle. Thus, we concluded that the studied compound has a pronounced inhibitory activity against group B enteroviruses not belonging to the class of capsid binder inhibitors, without virucidal properties. Previously, we described antioxidant properties of leucoverdazyls. It is known that many viral infections are accompanied by production of reactive oxygen species and oxidative stress, and some compounds with antioxidant properties exhibit antiviral potential. Targeted chemical modifications of leucoverdazyls and further studies of leucoverdazyl mechanism of action as well as in vivo animal studies are needed. However, the results obtained may be useful for future development of new antiviral drugs to treat enteroviral infections.

UR - https://elibrary.ru/item.asp?id=50455522

UR - http://www.scopus.com/inward/record.url?partnerID=8YFLogxK&scp=85153481344

U2 - 10.15789/2220-7619-VAL-2065

DO - 10.15789/2220-7619-VAL-2065

M3 - Article

VL - 13

SP - 107

EP - 118

JO - Russian Journal of Infection and Immunity

JF - Russian Journal of Infection and Immunity

SN - 2220-7619

IS - 1

ER -