Arbidol: a quarter-century after. Past, present and future of the original Russian antiviral

Balakin, Konstantin V.; Filosa, Rosanna; Лавренов, С. Н.; Mkrtchyan, A. S.; Nawrozkij, M. B.; Новаков, И. А.

doi:10.1070/rcr4791

Cited by 15 publications

(13 citation statements)

References 106 publications

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“…The half-life of the drug in the body is 17–21 h and ~40% is excreted in unchanged form. The formation of metabolites occurs by N -demethylation, S-oxidation, hydroxylation, O-glucuronide and O-sulfate conjugation ( Balakin et al, 2018 ; Wang et al, 2008 ; Deng et al, 2013 ). Thus, taking into account the incidence rate of coronavirus infection, the volumes of umifenovir and its metabolites entering municipal wastewater are quite large and for a city with a population of 1 million can reach several tens kg per day, even excluding consumption for the treatment of other viral diseases.…”

Section: Introductionmentioning

confidence: 99%

Antiviral drug Umifenovir (Arbidol) in municipal wastewater during the COVID-19 pandemic: Estimated levels and transformation

Ul’yanovskii

Kosyakov

Sypalov

et al. 2022

Science of The Total Environment

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An indole derivative umifenovir (Arbidol) is one of the most widely used antiviral drugs for the prevention and treatment of COVID-19 and some other viral infections. The purpose of the present study was to shed light on the transformation processes of umifenovir in municipal wastewater, including disinfection with active chlorine, as well as to assess the levels of the antiviral drug and its metabolites entering and accumulating in natural reservoirs under conditions of the SARS-CoV-2 pandemic. The combination of high-performance liquid chromatography with electrospray ionization high-resolution mass-spectrometry and inductively coupled plasma mass spectrometry was used for tentative identification and quantification of umifenovir and its transformation products in model reaction mixtures and real samples of wastewater, river water, biological sludge and bottom sediments taken at the wastewater treatment plant in Arkhangelsk, a large cultural and industrial center at the Russian North. Laboratory experiments allowed identifying fifteen bromine-containing transformation products, forming at the initial stages of the chlorination and fourteen classic volatile and semi volatile disinfection by-products with bromoform as the dominant one. Chlorinated derivatives are only the minor disinfection by-products forming by substitution of alkylamine group in the aromatic ring. The schemes of umifenovir transformation in reactions with dissolved oxygen and sodium hypochlorite are proposed. Two established primary transformation products formed by oxidation of the thioether group to sulfoxide and elimination of thiophenol were detected in noticeable concentrations in the wastewater together with their precursor. The level of umifenovir reached 1.3 mg kg −1 in the sludge and municipal wastewater treat contained 1 μg L −1 of that drug, while its removal during biological wastewater treatment was about 40%. Pronounced accumulation of umifenovir and its transformation products in biological sludge and bottom sediments of natural reservoirs may be a source of the future secondary pollution of the environment.

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Section: Introductionmentioning

confidence: 99%

Antiviral drug Umifenovir (Arbidol) in municipal wastewater during the COVID-19 pandemic: Estimated levels and transformation

Ul’yanovskii

Kosyakov

Sypalov

et al. 2022

Science of The Total Environment

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“…Subsequent bromination produced 37, which underwent thioetheri cation with 38 and in situ saponi cation to produce 39. Here, the route intercepts known syntheses of 2 via alkylation with 40 (30).…”

Section: Resultsmentioning

confidence: 99%

Reinforcing the Supply Chain of Umifenovir and Other Antiviral Drugs with Retrosynthetic Software

Lin

Zirong

Mahjour

et al. 2021

Preprint

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The global disruption caused by the 2020 coronavirus pandemic stressed the supply chain of many products, including pharmaceuticals. Multiple drug repurposing studies for COVID-19 are now underway. If a winning therapeutic emerges, it is unlikely that the existing inventory of the medicine, or even the chemical raw materials needed to synthesize it, will be available in the quantities required. We used retrosynthetic software to arrive at alternate chemical supply chains for the antiviral drug umifenovir, as well as eleven other antiviral and anti-inflammatory drugs. We have experimentally validated four routes to umifenovir and one route to bromhexine. In several instances, the software utilizes C–H functionalization logic, and one route to umifenovir employs functionalization of six C–H bonds. The general strategy we apply can be used to identify distinct starting materials, and relieve stress on existing supply chains.

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“…In 2011, the WHO rendered an international nonproprietary name Umifenovir to an active ingredient of arbidol but the original name given to this drug by its creators is still much more common and familiar both to patients and researchers. Up to now, its primary therapeutic action has not yet been known for certain: whether it is a direct antiviral activity, stimulation of immune system or anti-inflammatory action [60,61]. Agent EIDD-2801 works similarly to remdesivir, acting as nucleoside analogs that metabolize into an active form that blocks RNA polymerase, an essential component of viral replication.…”

Section: Promising Drug Candidates In the Fight Against Covid-19mentioning

confidence: 99%

COVID-19 treatment: Much research and testing, but far, few magic bullets against SARS-CoV-2 coronavirus

Kouznetsov

2020

European Journal of Medicinal Chemistry

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The new virus of the of b-Coronaviruses genus, SARS-CoV-2, is the causative agent of coronavirus disease-2019 (COVID-19) and is winning a proverbial chess match against all players simultaneous, including physicians, clinicians, pathologists, doctors, scientists, economists, athletes and politicians. The COVID-19 outbreak has seriously threatened public health, killing the most vulnerable persons and causing general panic. To stop this disease, effective remedies (i.e., drugs, vaccines, personal protection elements, etc.) are urgently required. Unfortunately, no registered specific therapies (including antiviral therapies, immune-modulating agents and vaccines) are currently available to treat coronavirus infections, highlighting an urgent need for therapeutics targeting SARS-CoV-2. In this work, fourteen existing small molecule drugs or/and experimental drugs selected by experts and examined from the point of view of bioavailability via the Lipinski-Veber rules and assessment of their physicochemical descriptors. The aim of this study is to discover selected pattern similarities and peculiar characteristics that could be useful for antiviral drug optimization, drug combination or new antiviral agent design.

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Arbidol: a quarter-century after. Past, present and future of the original Russian antiviral

Cited by 15 publications

References 106 publications

Antiviral drug Umifenovir (Arbidol) in municipal wastewater during the COVID-19 pandemic: Estimated levels and transformation

Antiviral drug Umifenovir (Arbidol) in municipal wastewater during the COVID-19 pandemic: Estimated levels and transformation

Reinforcing the Supply Chain of Umifenovir and Other Antiviral Drugs with Retrosynthetic Software

COVID-19 treatment: Much research and testing, but far, few magic bullets against SARS-CoV-2 coronavirus

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