Monoterpenoid-based inhibitors of filoviruses targeting the glycoprotein-mediated entry process

Соколова, А. С.; Yarovaya, Оlga I.; Zybkina, Anastasiya V.; Mordvinova, Ekaterina D.; Shcherbakova, N. S.; Zaykovskaya, А. V.; Baev, Dmitry S.; Толстикова, Т. Г.; Щербаков, Д. Н.; Pyankov, Oleg V.; Maksyutov, Rinat А.; Salakhutdinov, N. F.

doi:10.1016/j.ejmech.2020.112726

Cited by 29 publications

(24 citation statements)

References 26 publications

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“…Target borneol derivatives were synthesised via a sequence of reactions starting with commercially available (-)-borneol. Borneol derivatives 8a-c and 9a-c with a tertiary amino group were prepared in two steps as described previously [ 19 ]. Subsequent methylation, using iodomethane under reflux, gave the corresponding quaternary ammonium salts 10a, 10c and 11a-b (Scheme 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…All of the target compounds reported in this publication were of at least 98% purity. The synthesis of derivatives 1 and 2 [ 11 ] and 8a-c and 9a-c [ 19 ] were described previously. Compounds 6-7, 10a and c, and 11a and b, have not been described previously in the literature.…”

Section: Methodsmentioning

confidence: 99%

“…We have discovered several borneol esters with activity against Ebola virus (EBOV), Marburg virus (MARV), and influenza virus – for example, compounds 4 and 5 [ 16 – 18 ]. Moreover, we have shown that the possible mechanism of inhibition of EBOV is binding to the active site of the EBOV glycoprotein [ 19 ]. Members of the family Filoviridae , including EBOV and MARV, and of the family Orthomyxoviridae , including influenza virus, have class I fusion proteins with similar pre- and post-fusion forms [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Quaternary ammonium salts based on (-)-borneol as effective inhibitors of influenza virus

et al. 2021

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A series of compounds containing a 1,7,7-trimethylbicyclo[2.2.1]heptane fragment were evaluated for their antiviral activity against influenza A virus strain A/Puerto Rico/8/34 (H1N1) in vitro . The most potent antiviral compound proved to be a quaternary ammonium salt based on (-)-borneol, 10a. In in vitro experiments, compound 10a inhibited influenza A viruses (H1, H1pdm09, and H3 subtypes), with an IC 50 value of 2.4-16.8 µM (depending on the virus), and demonstrated low toxicity (CC 50 = 1311 µM). Mechanism-of-action studies for compound 10a revealed it to be most effective when added at the early stages of the viral life cycle. In direct haemolysis inhibition tests, compound 10a was shown to decrease the membrane-disrupting activity of influenza A virus strain A/Puerto Rico/8/34. According to molecular modelling results, the lead compound 10a can bind to different sites in the stem region of the viral hemagglutinin. Supplementary Information The online version contains supplementary material available at 10.1007/s00705-021-05102-1.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Quaternary ammonium salts based on (-)-borneol as effective inhibitors of influenza virus

et al. 2021

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“…Target borneol derivatives were synthesized via a sequence of reactions starting with a commercially available (-)-borneol. Borneol derivatives 8a-c and 9a-c with tertiary amino group were prepared in two steps as previously described [18]. Subsequent methylation, using iodomethane under re ux, gave corresponding quaternary ammonium salts 10a, 10c and 11a-b (Scheme 2).…”

Section: Chemistrymentioning

confidence: 99%

“…We discovered several borneol ester molecules with activity against Ebola virus (EBOV) and Marburg virus (MARV) and in uenza virus, for example, compounds 4-5 [ 15,16,17 ]. Moreover, we have shown that the possible mechanism of inhibition of EBOV is binding to the active site of EBOV glycoprotein [ 18 ]. The lovirus family, which includes EBOV and MARV, and the orthomyxovirus family, which includes the in uenza virus, belong to class I fusion proteins and have similar pre-and post-fusion forms [ 19 ].…”

Section: Introductionmentioning

confidence: 98%

Quaternary Ammonium Salts Based on (-)-Borneol as Effective Inhibitors of Influenza Virus

Соколова

Yarovaya

Baranova

et al. 2021

Preprint

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A new compounds containing 1,7,7-trimethylbicyclo[2.2.1]heptane fragment has been found to exhibit potent inhibitory activity against the influenza A(H1N1) virus. The most potent antiviral compound 10a is a quaternary ammonium salt based on (-)-borneol, with a therapeutic index of more than 500. Mechanism-of-action studies for compound 10a were performed. The compound appeared the most effective when added at the early stages of viral life cycle. In direct hemagglutinin inhibition tests the agent, 10a, was shown to decrease the activity of hemagglutinin of influenza virus A/Puerto Rico/8/34. According to the results of molecular modelling, the lead-compound, 10a, can attach at the binding sites of the stem part of the HA. These results prove that monoterpenoids with 1,7,7-trimethylbicyclo[2.2.1]heptane fragment are prospective natural compounds for the development of antiviral agents.

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(+)‐Camphor and (−)‐borneol derivatives as potential anti‐orthopoxvirus agents

Соколова

Kovaleva

Yarovaya

et al. 2021

Archiv der Pharmazie

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Although the World Health Organisation had announced that smallpox was eradicated over 40 years ago, the disease and other related pathogenic poxviruses such as monkeypox remain potential bioterrorist weapons and could also re-emerge as natural infections. We have previously reported (+)-camphor and (−)-borneol derivatives with an antiviral activity against the vaccinia virus. This virus is similar to the variola virus (VARV), the causative agent of smallpox, but can be studied at BSL-2 facilities. In the present study, we evaluated the antiviral activity of the most potent compounds against VARV, cowpox virus, and ectromelia virus (ECTV). Among the compounds tested, 4-bromo-Nʹ-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2ylidene)benzohydrazide 18 is the most effective compound against various orthopoxviruses, including VARV, with an EC 50 value of 13.9 μM and a selectivity index of 206. Also, (+)-camphor thiosemicarbazone 9 was found to be active against VARV and ECTV.

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Monoterpenoid-based inhibitors of filoviruses targeting the glycoprotein-mediated entry process

Cited by 29 publications

References 26 publications

Quaternary ammonium salts based on (-)-borneol as effective inhibitors of influenza virus

Quaternary ammonium salts based on (-)-borneol as effective inhibitors of influenza virus

Quaternary Ammonium Salts Based on (-)-Borneol as Effective Inhibitors of Influenza Virus

(+)‐Camphor and (−)‐borneol derivatives as potential anti‐orthopoxvirus agents

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