To date, the ‘one bug-one drug’ approach to antiviral drug development cannot effectively respond to the constant threat posed by an increasing diversity of viruses causing outbreaks of viral infections that turn out to be pathogenic for humans. Evidently, there is an urgent need for new strategies to develop efficient antiviral agents with broad-spectrum activities. In this paper, we identified camphene derivatives that showed broad antiviral activities in vitro against a panel of enveloped pathogenic viruses, including influenza virus A/PR/8/34 (H1N1), Ebola virus (EBOV), and the Hantaan virus. The lead-compound 2a, with pyrrolidine cycle in its structure, displayed antiviral activity against influenza virus (IC₅₀ = 45.3 µM), Ebola pseudotype viruses (IC₅₀ = 0.12 µM), and authentic EBOV (IC₅₀ = 18.3 µM), as well as against pseudoviruses with Hantaan virus Gn-Gc glycoprotein (IC₅₀ = 9.1 µM). The results of antiviral activity studies using pseudotype viruses and molecular modeling suggest that surface proteins of the viruses required for the fusion process between viral and cellular membranes are the likely target of compound 2a. The key structural fragments responsible for efficient binding are the bicyclic natural framework and the nitrogen atom. These data encourage us to conduct further investigations using bicyclic monoterpenoids as a scaffold for the rational design of membrane-fusion targeting inhibitors.

In the present work we studied the antiviral activity of the home library of monoterpenoid derivatives using the pseudoviral systems of our development, which have glycoproteins of the SARS-CoV-2 virus strains Wuhan and Delta on their surface. We found that borneol derivatives with a tertiary nitrogen atom can exhibit activity at the early stages of viral replication. In order to search for potential binding sites of ligands with glycoprotein, we carried out additional biological tests to study the inhibition of the re-receptor-binding domain of protein S. For the compounds that showed activity on the pseudoviral system, a study using three strains of the infectious SARS-CoV-2 virus was carried out. As a result, two leader compounds were found that showed activity on the Wuhan, Delta, and Omicron strains. Based on the biological results, we searched for the potential binding site of the leader compounds using molecular dynamics and molecular docking methods. We suggested that the compounds can bind in conserved regions of the central helices and/or heptad repeats of glycoprotein S of SARS-CoV-2 viruses.

In this work, we evaluated the antiviral activity of Arbidol (Umifenovir) against SARS-CoV-2 using a pseudoviral system with the glycoprotein S of the SARS-CoV-2 virus on its surface. In order to search for binding sites to protein S of the virus, we described alternative binding sites of Arbidol in RBD and in the ACE-2-RBD complex. As a result of our molecular dynamics simulations combined with molecular docking data, we note the following fact: wherever the molecules of Arbidol bind, the interaction of the latter affects the structural flexibility of the protein. This interaction may result both in a change in the shape of the domain–enzyme binding interface and simply in a change in the structural flexibility of the domain, which can subsequently affect its affinity to the enzyme. In addition, we examined the possibility of Arbidol binding in the stem part of the surface protein. The possibility of Arbidol binding in different parts of the protein is not excluded. This may explain the antiviral activity of Arbidol. Our results could be useful for researchers searching for effective SARS-CoV-2 virus inhibitors targeting the viral entry stage.

A set of heterocyclic products was synthesized from natural (+)-camphor and semi-synthetic (−)-camphor. Then, 2-Imino-4-thiazolidinones and 2,3-dihydrothiazoles were obtained using a three-step procedure. For the synthesized compounds, their antiviral activity against the vaccinia virus and Marburg virus was studied. New promising agents active against both viruses were found among the tested compounds.

Angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV-2, plays a crucial role in the pathogenesis of COVID-19. ACE2 targeting holds the promise for preventing and inhibiting SARS-CoV-2 infection. In this work, we describe the development and use of a test system based on competitive ELISA for the primary screening of potential antiviral compounds. We studied the activity of the library of dyes of different groups. Several dyes (ortho-cresolphthalein, eosin (free acid), eosin (Na salt)) that inhibited the interaction of ACE2 with the spike proteins of SARS-CoV-2 have been identified among the candidates. A potential antiviral drug, methylene blue, did not show activity in our study. We believe that our results can help in the further search for inhibitors of interaction between the coronavirus spike protein and ACE2 receptor.

Изучен состав липофильных компонентов растения Rhodiola rosea L. Кислые и нейтральные компоненты идентифицировали при помощи газожидкостной хроматографии с масс-спектрометрической детекцией. В качестве экстрагента сырья использован метил-трет-бутиловый эфир (МТБЭ), обладающий всеми достоинствами диэтилового эфира, но лишенный его недостатков. Он не образует перекисей и не создает повышенной загазованности за счет более высокой температуры кипения. В результате сравнением с базами данных идентифицированы тритерпеновые, фенолкарбоновые и алифатические кислоты с длиной цепи от 8 до 30 атомов углерода, включая насыщенные, ненасыщенные и двухосновные кислоты. В дополнение к компонентам, известным из литературы, впервые идентифицировано более 50 тритерпеновых и алифатических компонентов неомыляемого остатка и кислых фракций. Аналогично исследованы гексановый экстракт и продукт, полученный ступенчатой экстракцией МТБЭ после извлечения малополярных соединений гексаном. В случае экстракта, полученного при помощи МТБЭ после экстракции сырья гексаном, выявлено более эффективное извлечение фенольных кислот бензойного и коричного ряда по сравнению с исчерпывающей экстракцией МТБЭ. В гексановом экстракте эти кислоты отсутствуют. Для проведения тестирования биоактивности проведена экстракция этанолом: исчерпывающая и после экстракции гексаном и МТБЭ. Экстракты Rhodiola rosea L., полученные при помощи МТБЭ и этанола, проявили антивирусную активность в отношении псевдовирусов Эбола.