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.

The influenza virus genome features a very high mutation rate leading to the rapid selection of drug-resistant strains. Due to the emergence of drug-resistant strains, there is a need for the further development of new potent antivirals against influenza with a broad activity spectrum. Thus, the search for a novel, effective broad-spectrum antiviral agent is a top priority of medical science and healthcare systems. In this paper, derivatives based on fullerenes with broad virus inhibiting activities in vitro against a panel of influenza viruses were described. The antiviral properties of water-soluble fullerene derivatives were studied. It was demonstrated that the library of compounds based on fullerenes has cytoprotective activity. Maximum virus-inhibiting activity and minimum toxicity were found with compound 2, containing residues of salts of 2-amino-3-cyclopropylpropanoic acid (CC₅₀ > 300 µg/mL, IC₅₀ = 4.73 µg/mL, SI = 64). This study represents the initial stage in a study of fullerenes as anti-influenza drugs. The results of the study lead us conclude that five leading compounds (1–5) have pharmacological prospects.

New unsymmetrical monoterpenylhetaryl disulfides based on heterocyclic disulfides and monoterpene thiols were synthesized for the first time in 48–88% yields. Hydrolysis of disulfides with fragments of methyl esters of 2-mercaptonicotinic acid was carried out in 73–95% yields. The obtained compounds were evaluated for antioxidant, antibacterial, antifungal activity, cytotoxicity and mutagenicity.

A series of pyrimidine conjugates containing a fragment of racemic 7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine and its (S)-enantiomer attached via a 6-aminohexanoyl fragment were synthesized by the reaction of nucleophilic substitution of chlorine in various chloropyrimidines. The structures of the synthesized compounds were confirmed by ¹H, ¹⁹F, and ¹³C NMR spectral data. Enantiomeric purity of optically active derivatives was confirmed by chiral HPLC. Antiviral evaluation of the synthesized compounds has shown that the replacement of purine with a pyrimidine fragment leads to a decrease in the anti-herpesvirus activity compared to the lead compound, purine conjugate. The studied compounds did not exhibit significant activity against influenza A (H1N1) virus.

New 1′-homocarbanucleoside analogs with an optically active substituted bicyclo[2.2.1]heptane skeleton as sugar moiety were synthesized. The pyrimidine analogs with uracil, 5-fluorouracil, thymine and cytosine and key intermediate with 6-chloropurine (5) as nucleobases were synthesized by a selective Mitsunobu reaction on the primary hydroxymethyl group in the presence of 5-endo-hydroxyl group. Adenine and 6-substituted adenine homonucleosides were obtained by the substitution of the 6-chlorine atom of the key intermediate 5 with ammonia and selected amines, and 6-methoxy- and 6-ethoxy substituted purine homonucleosides by reaction with the corresponding alkoxides. No derivatives appeared active against entero, yellow fever, chikungunya, and adeno type 1viruses. Two compounds (6j and 6d) had lower IC₅₀ (15 ± 2 and 21 ± 4 µM) and compound 6f had an identical value of IC₅₀ (28 ± 4 µM) to that of acyclovir, suggesting that the bicyclo[2.2.1]heptane skeleton could be further studied to find a candidate for sugar moiety of the nucleosides.

An optically active bicyclo[2.2.0]heptane fragment was introduced in the molecule of new 1′-homonucleosides on a 2- 6-chloro-amino-purine scaffold to obtain 6-substituted carbocyclicnucleozide analogs as antiviral compounds. The synthesis was realized by a Mitsunobu reaction of the base with the corresponding bicyclo[2.2.0]heptane intermediate, and then the nucleoside analogs were obtained by substitution of the 6-chlorime with selected pharmaceutically accepted amines. A molecular docking study of the compounds on influenza, HSV and low active coronavirus was realized. Experimental screening of the compounds on the same viruses is being developed and soon will be finished.