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1.
Biomolecules ; 11(12)2021 12 10.
Article in English | MEDLINE | ID: covidwho-1572360

ABSTRACT

Metal-based drugs represent a rich source of chemical substances of potential interest for the treatment of COVID-19. To this end, we have developed a small but representative panel of nine metal compounds, including both synthesized and commercially available complexes, suitable for medical application and tested them in vitro against the SARS-CoV-2 virus. The screening revealed that three compounds from the panel, i.e., the organogold(III) compound Aubipyc, the ruthenium(III) complex KP1019, and antimony trichloride (SbCl3), are endowed with notable antiviral properties and an acceptable cytotoxicity profile. These initial findings prompted us to perform a computational study to unveil the likely molecular basis of their antiviral actions. Calculations evidenced that the metalation of nucleophile sites in SARS-CoV-2 proteins or nucleobase strands, induced by Aubipyc, SbCl3, and KP1019, is likely to occur. Remarkably, we found that only the deprotonated forms of Cys and Sec residues can react favorably with these metallodrugs. The mechanistic implications of these findings are discussed.


Subject(s)
2,2'-Dipyridyl/analogs & derivatives , Antimony/pharmacology , Antiviral Agents/pharmacology , COVID-19/drug therapy , Chlorides/pharmacology , Indazoles/pharmacology , Organogold Compounds/pharmacology , Organometallic Compounds/pharmacology , Ruthenium Compounds/pharmacology , SARS-CoV-2/drug effects , 2,2'-Dipyridyl/chemistry , 2,2'-Dipyridyl/pharmacology , Animals , Antimony/chemistry , Antiviral Agents/chemistry , Cell Line , Chlorides/chemistry , Chlorocebus aethiops , Drug Discovery , Humans , Indazoles/chemistry , Organogold Compounds/chemistry , Organometallic Compounds/chemistry , Ruthenium Compounds/chemistry , Vero Cells
2.
Viruses ; 13(12)2021 12 04.
Article in English | MEDLINE | ID: covidwho-1554971

ABSTRACT

Epidemic RNA viruses seem to arise year after year leading to countless infections and devastating disease. SARS-CoV-2 is the most recent of these viruses, but there will undoubtedly be more to come. While effective SARS-CoV-2 vaccines are being deployed, one approach that is still missing is effective antivirals that can be used at the onset of infections and therefore prevent pandemics. Here, we screened FDA-approved compounds against SARS-CoV-2. We found that atovaquone, a pyrimidine biosynthesis inhibitor, is able to reduce SARS-CoV-2 infection in human lung cells. In addition, we found that berberine chloride, a plant-based compound used in holistic medicine, was able to inhibit SARS-CoV-2 infection in cells through direct interaction with the virion. Taken together, these studies highlight potential avenues of antiviral development to block emerging viruses. Such proactive approaches, conducted well before the next pandemic, will be essential to have drugs ready for when the next emerging virus hits.


Subject(s)
Antiviral Agents/pharmacology , Atovaquone/pharmacology , Berberine/pharmacology , SARS-CoV-2/drug effects , Virus Replication/drug effects , Alveolar Epithelial Cells , Animals , Berberine/chemistry , Cell Proliferation/drug effects , Chlorides/chemistry , Chlorides/pharmacology , Chlorocebus aethiops , Drug Synergism , Humans , Proguanil/pharmacology , Vero Cells , Virion/drug effects
3.
Hosp Pract (1995) ; 48(4): 165-168, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-919318

ABSTRACT

Limited availability of personal protective equipment is endangering first-line health-care providers treating patients with presumed or confirmed COVID-19 infections. This editorial has multiple objectives in regard to this reality: First, to raise awareness of the need for safe and effective prophylaxis to protect health-care providers with insufficient personal protective equipment from repeated exposures to COVID-19. Second, to summarize the scientific evidence in support of solutions of acidified sodium chlorite (ASC) and its daughter compounds, chlorous acid and chlorine dioxide, as potential targets for said prophylactic use. Third, to propose a regimented protocol using commercially available solutions of ASC having sufficient concentrations of chlorine dioxide for virucidal activity to support safe and effective prophylactic use. And fourth, to raise awareness of and compare other potential prophylactic options currently under investigation.


Subject(s)
Betacoronavirus/drug effects , Chlorides/administration & dosage , Chlorides/pharmacology , Coronavirus Infections/transmission , Disease Transmission, Infectious/prevention & control , Medical Staff, Hospital , Pneumonia, Viral/transmission , Pre-Exposure Prophylaxis/standards , COVID-19 , Chlorides/chemistry , Drug Tolerance , Humans , Pandemics , SARS-CoV-2
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