WHO reports that 90% of human population is infected by different types of herpesviruses, which develop latency or cause oral and genital herpes, conjunctivitis, eczema herpeticum, and other diseases. Herpesvirus almost always accompanies HIV-infection and complicates AIDS treatment. Herpes simplex virus type 1 is one of the most wide spread viruses from the Herpesviridae family. HSV virion, genome structure, replication mechanisms, antiherpes drug development strategies, including design of prodrugs, and mutations causing ACV-resistance in clinical HSV isolates are discussed in this review.

This short review is focused on enzymatic properties of human ATP-dependent RNA helicase DDX3 and the development of antiviral and anticancer drugs targeting cellular helicases. DDX3 belongs to the DEAD-box proteins, a large family of RNA helicases that participate in all aspects of cellular processes, such as cell cycle progression, apoptosis, innate immune response, viral replication, and tumorigenesis. DDX3 has a variety of functions in the life cycle of different viruses. DDX3 helicase is required to facilitate both the Rev-mediated export of unspliced/partially spliced human immunodeficiency virus (HIV) RNA from nucleus and Tat-dependent translation of viral genes. DDX3 silencing blocks the replication of HIV, HCV, and some other viruses. On the other hand, DDX displays antiviral effect against Dengue virus and hepatitis B virus through the stimulation of interferon beta production. The role of DDX3 in different types of cancer is rather controversial. DDX3 acts as an oncogene in one type of cancer, but demonstrates tumor suppressor properties in other types. The human DDX3 helicase is now considered as a new attractive target for the development of novel pharmaceutical drugs. The most interesting inhibitors of DDX3 helicase and the mechanisms of their actions as antiviral or anticancer drugs are discussed in this short review.

Influenza viruses of types A and B cause periodic pandemics in the human population. The antiviral drugs approved to combat influenza virus infections are currently limited. We have investigated an effective novel inhibitor of human influenza A and B viruses, triazavirine {2-methylthio-6-nitro-1,2,4-triazolo[5,1-c]-1,2,4-triazine-7(4Í)-one} (TZV). TZV suppressed the replication of influenza virus in cell culture and in chicken chorioallantoic membranes, and it protected mice from death caused by type A and B influenza viruses. TZV was also effective against a rimantadine-resistant influenza virus strain and against avian influenza A virus H5N1 strains. The pharmacokinetic parameters and bioavailability of TZV were calculated after the administration of TZV to rabbits. The TZV metabolite AMTZV {2-methylthio-6-amino-1,2,4-triazolo[5,1- s ]-1,2,4-triazin(e)-7(4Í)-one} was discovered in ÍÅK 293T and Huh7 cell cultures, a liver homogenate, and rabbit blood after intragastric administration of TZV. AMTZV was nontoxic and inactive as an inhibitor of influenza virus in cell culture. Most likely, this metabolite is a product of TZV elimination.

The review considers the design of antiretroviral drugs based on nucleoside analogs. Approximately 30 drugs have been approved for treating HIV-infected patients over the past 25 years. Seven nucleoside drugs act as HIV reverse transcriptase (RT) inhibitors and are clinically used in combination with inhibitors of other viral enzymes, integrase and protease, and nonnucleoside inhibitors of HIV RT. Toxicity of nucleoside drugs and the possibility to obtain safe anti-HIV drugs by constructing their depot forms are discussed. The results of developing anti-HIV drugs in Russia are described. The future prospects of anti-HIV research are considered.

A series of new 5′‐O‐carbamate prodrugs of AZT have been prepared. The stability in biological media, anti‐HIV properties and pharmacokinetic parameters in dogs were evaluated. The compounds display moderate anti‐HIV activity in cell culture. After oral administration of carbamate IV in dogs, both intact prodrug IV and released AZT were discovered in dog blood. Pharmacokinetic parameters of the compound IV were estimated. Half‐life (T_1/2) of AZT released after oral administration of IV in dogs was close to that after administration of AZT itself, and time to the maximum concentration (T_max) of AZT released from IV was two and three times longer compared with that of AZT and H‐phosphonate AZT, respectively. Acute toxicity was more than five times less if compared with AZT. As a result, we consider this series of carbamate derivatives of AZT as perspective for development of anti‐HIV agents.