The rapid emergence of drug-resistant strains and novel viruses have motivated the search for new anti-infectious agents. In this study, the chemical compositions and cytotoxicity, as well as the antibacterial, antifungal, antitrichomonas, and antiviral activities of essential oils from the leaves, rhizomes, and whole plant of Hornstedtia bella were investigated. The GC/MS analysis showed that β-pinene, E-β-caryophyllene, and α-humulene were found at high concentrations in the essential oils. The essential oils exhibited (i) inhibition against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis with minimum inhibitory concentrations (MIC) and minimum lethal concentration (MLC) values from 1 to 4% (v/v); (ii) MIC and MLC values from 2 to 16% (v/v) in Candida tropicalis and Candida parapsilosis; (iii) MIC and MLC values from 4 to 16% in Enterococcus faecalis; and (iv) MIC and MLC values from 8 to greater than or equal to 16% (v/v) in the remaining strains, including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Candida albicans, and Candida glabrata. In antitrichomonas activity, the leaves and whole-plant oils of Hornstedtia bella possessed IC₅₀, IC₉₀, and MLC values of 0.008%, 0.016%, and 0.03% (v/v), respectively, whilst those of rhizomes oil had in turn, 0.004%, 0.008%, and 0.016% (v/v).Besides, the leaf oil showed a weak cytotoxicity against Vero 76 and MRC-5; meanwhile, rhizomes and whole-plant oils did not exert any toxic effects on cell monolayers. Finally, these oils were not active against EV-A71.

A series of 2-(1H-indol-3-yl)ethylthiourea derivatives were prepared by condensation of 2-(1H-indol-3-yl)ethanamine with appropriate aryl/alkylisothiocyanates in anhydrous media. The structures of the newly synthesized compounds were confirmed by spectroscopic analysis and the molecular structures of 8 and 28 were confirmed by X-ray crystallography. All obtained compounds were tested for antimicrobial activity against Gram-positive cocci, Gram-negative rods and for antifungal activity. Microbiological evaluation was carried out over 20 standard strains and 30 hospital strains. Compound 6 showed significant inhibition against Gram-positive cocci and had inhibitory effect on the S. aureus topoisomerase IV decatenation activity and S. aureus DNA gyrase supercoiling activity. Compounds were tested for cytotoxicity and antiviral activity against a large panel of DNA and RNA viruses, including HIV-1 and other several important human pathogens. Interestingly, derivative 8 showed potent activity against HIV-1 wild type and variants bearing clinically relevant mutations. Newly synthesized tryptamine derivatives showed also a wide spectrum activity, proving to be active against positive- and negative-sense RNA viruses.

The present study aimed to determine the antimicrobial activity and chemical composition of leaves-extracted essential oil of Leoheo domatiophorus Chaowasku, D.T. Ngo and H.T. Le (L. domatiophorus), including antibacterial, antimycotic, antitrichomonas and antiviral effects. The essential oil was obtained using hydrodistillation, with an average yield of 0.34 ± 0.01% (v/w, dry leaves). There were 52 constituents as identified by GC/MS with available authentic standards, representing 96.74% of the entire leaves oil. The essential oil was comprised of three main components, namely viridiflorene (16.47%), (-)-δ-cadinene (15.58%) and γ-muurolene (8.00%). The oil showed good antimicrobial activities against several species: Gram-positive strains: Staphylococcus aureus (two strains) and Enterococcus faecalis, with Minimum Inhibitory Concentration (MIC) and Minimum Lethal Concentration (MLC) values from 0.25 to 1% (v/v); Gram-negative strains such as Escherichia coli (two strains), Pseudomonas aeruginosa (two strains) and Klebsiella pneumoniae, with MIC and MLC values between 2% and 8% (v/v); and finally Candida species, having MIC and MLC between 0.12 and 4% (v/v).Antitrichomonas activity of the oil was also undertaken, showing IC₅₀, IC₉₀ and MLC values of 0.008%, 0.016% and 0.03% (v/v), respectively, after 48h of incubation. The essential oil resultedin being completely ineffective against tested viruses, ssRNA+ (HIV-1, YFV, BVDV, Sb-1, CV-B4), ssRNA- (hRSVA2, VSV), dsRNA (Reo-1), and dsDNA (HSV-1, VV) viruses with EC₅₀ values over 100 µg/mL. This is the first, yet comprehensive, scientific report about the chemical composition and pharmacological properties of the essential oil in L. domatiophorus.

Enterovirus A71 (EV-A71) infection has emerged as a significant public health concern at the global level. Epidemic events of EV-A71 have been reported worldwide, and this succession of outbreaks has heightened concern that EV-A71 may become a public health threat. In recent years, widespread A71 enterovirus also occurred in European countries. EV-A71 infection causes hand-foot-mouth disease (HFMD), herpangina, and fever. However, it can sometimes induce a variety of neurological complications, including encephalitis, aseptic meningitis, pulmonary edema, and acute flaccid paralysis. We identified new benzimidazole derivatives and described theirin vitrocytotoxicity and broad-spectrum anti-enterovirus activity. Among them, derivative 2b resulted in interesting activity against EV-A71, and therefore it was selected for further investigations. Compound 2b proved to be able to protect cell monolayers from EV-A71-induced cytopathogenicity, with an EC₅₀ of 3 µM. Moreover, Vero-76 cells resulted in being significantly protected from necrosis and apoptosis when treated with 2b at 20 and 80 µM. Compound 2b reduced viral adsorption to Vero-76 cells, and when evaluated in a time-of-addition assay, the derivative had the highest effect when added during the infection period. Moreover, derivative 2b reduced viral penetration into host cells. Besides, 2b did not affect intestinal monolayers permeability, showing no toxic effects. A detailed insight into the efficacy of compound 2b against EV-A71 showed a dose-dependent reduction in the viral titer, also at low concentrations. Mechanism of action investigations suggested that our derivative can inhibit viral endocytosis by reducing viral attachment to and penetration into host cells. Pharmacokinetic and toxicity predictions validated compound 2b as a good candidate for furtherin vivoassays.

Orthohantaviruses, previously known as hantaviruses (family Hantaviridae, order Bunyavirales), are emerging zoonoses hosted by different rodent and insectivore species. Orthohantaviruses are transmitted by aerosolized excreta (urine, saliva and feces) of their reservoir hosts. When transmitted to humans, they cause hemorrhagic fever with renal syndrome (HFRS) in Asia and Europe and hantavirus (cardio) pulmonary syndrome (HPS) in the Americas. Clinical studies have shown that early treatments of HFRS patients with ribavirin (RBV) improve prognosis. Nevertheless, there is the need for urgent development of specific antiviral drugs. In the search for new RNA virus inhibitors, we recently identified a series of variously substituted 5,6-dichloro-1(2)-phenyl-1(2)H-benzo[d][1,2,3]triazole derivatives active against the human respiratory syncytial virus (HRSV). Interestingly, several 2-phenyl-benzotriazoles resulted in fairly potent inhibitors of the Hantaan virus in a chemiluminescence focus reduction assay (C-FRA) showing an EC₅₀ = 4–5 µM, ten-fold more active than ribavirin. Currently, there are no FDA approved drugs for the treatment of orthohantavirus infections. Antiviral activities and cytotoxicity profiles suggest that 5,6-dichloro-1(2)-phenyl-1(2)H-benzo[d][1,2,3]triazoles could be promising candidates for further investigation as a potential treatment of hantaviral diseases.

Plant products provide an alternative and successful source of lead compounds for the pharmaceutical industry. The present study was aimed to evaluate, in cell-based assays, the antiviral properties of essential oils obtained from plants that commonly grow in Sardinia, Italy, against a broad spectrum of RNA/DNA viruses. The essential oils of Helichrisumitalicum (Roth) G. Don ssp. microphyllum (Willd.) Nyman, Laurus nobilis L., Mirtuscommunis L., Pistacia lentiscus L., Salvia officinalis L., Saturejathymbra L., Lavandula angustifolia Mill., Foeniculum vulgare Mill., and Eucalyptus globulus Labill. were extracted by hydrodistillation and analyzed by gas chromatography mass spectrometry (GC–MS). Interestingly, the essential oil of Salvia officinalis showed moderate activity against bovine viral diarrhea virus (BVDV), an enveloped RNA virus belonging to the Flaviviridae family. BVDV is responsible for several clinical manifestations in bovines, including respiratory, gastroenteric, and reproductive diseases, with a significant economic impact. With the aim to individuate the constituent of the Salvia officinalis responsible for the biological activity, we tested the major components of the oil: camphene, β-pinene, limonene, 1,8-cineole, cis-thujone, camphor, (E)-caryophyllene, and α-humulene. Here, we describe α-humulene as an active component that is non-cytotoxic and active against BVDV (EC₅₀ = 36 µM). Its antiviral effects were evaluated using virucidal cytopathic effect inhibition and viral yield reduction assays. This is the first scientific report showing the anti BVDV effects of Salvia officinalis essential oil and α-humulene as the main active component.