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BMC Res Notes ; 13(1): 527, 2020 Nov 11.
Article in English | MEDLINE | ID: covidwho-917943


OBJECTIVES: The aim of this study was to use Ligand-based pharmacophore modelling approach for four established antiviral drugs, namely remdesivir, lopinavir, ritonavir and hydroxychloroquine for COVID-19 inhibitors as training sets. In this study Twenty vanillin derivatives together with monolaurin and tetrodotoxin were used as test sets to evaluate as potential SARS-CoV-2 inhibitors. The Structure-based pharmacophore modelling approach was also performed using 5RE6, 5REX and 5RFZ in order to analyse the binding site and ligand-protein complex interactions. RESULTS: The pharmacophore modelling mode of 5RE6 displayed two Hydrogen Bond Acceptors (HBA) and one Hydrophobic (HY) interaction. Besides, the pharmacophore model of 5REX showed two HBA and two HY interactions. Finally, the pharmacophore model of 5RFZ showed three HBA and one HY interaction. Based on ligand-based approach, 20 Schiff-based vanillin derivatives, showed strong MPro inhibition activity. This was due to their good alignment and common features to PDB-5RE6. Similarly, monolaurin and tetrodotoxin displayed some significant activity against SARS-CoV-2. From structure-based approach, vanillin derivatives (1) to (12) displayed some potent MPro inhibition against SARS-CoV-2. Favipiravir, chloroquine and hydroxychloroquine also showed some significant MPro inhibition.

Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Chloroquine/pharmacology , Cysteine Proteinase Inhibitors/pharmacology , Viral Nonstructural Proteins/antagonists & inhibitors , Amides/chemistry , Amides/pharmacology , Antiviral Agents/chemistry , Benzaldehydes/chemistry , Chloroquine/chemistry , Computer Simulation , Coronavirus 3C Proteases , Cysteine Endopeptidases , Cysteine Proteinase Inhibitors/chemistry , Humans , Hydroxychloroquine/chemistry , Hydroxychloroquine/pharmacology , Laurates/chemistry , Laurates/pharmacology , Microbial Sensitivity Tests , Models, Molecular , Monoglycerides/chemistry , Monoglycerides/pharmacology , Pyrazines/chemistry , Pyrazines/pharmacology , SARS-CoV-2 , Structure-Activity Relationship , Tetrodotoxin/chemistry , Tetrodotoxin/pharmacology
mSphere ; 5(4)2020 07 29.
Article in English | MEDLINE | ID: covidwho-726126


Staphylococcus aureus is a highly significant infection problem in health care centers, particularly after surgery. It has been shown that nearly 80% of S. aureus infections following surgery are the same as those in the anterior nares of patients, suggesting that the anterior nares is the source of the infection strain. This has led to the use of mupirocin ointment being applied nasally to reduce infections; mupirocin resistance is being observed. This study was undertaken to determine whether gel composed of 5% glycerol monolaurate solubilized in a glycol-based, nonaqueous gel (5% GML gel) could be used as an alternative. In our study, 40 healthy human volunteers swabbed their anterior nares for 3 days with the 5% GML gel. Prior to swabbing and 8 to 12 h after swabbing, S. aureus and coagulase-negative staphylococcal CFU per milliliter were determined by plating the swabs on mannitol salt agar. Fourteen of the volunteers had S. aureus in their nares prior to 5% GML gel treatment, most persons with the organisms present in both nares; five had pure cultures of S. aureus All participants without pure culture of S. aureus were cocolonized with S. aureus and coagulase-negative staphylococci. Five of the S. aureus strains produced the superantigens commonly associated with toxic shock syndrome, though none of the participants became ill. For both S. aureus and coagulase-negative staphylococci, the 5% GML gel treatment resulted in a 3-log-unit reduction in microorganisms. For S. aureus, the reduction persisted for 2 or 3 days.IMPORTANCE In this microflora study, we show that a 5% glycerol monolaurate nonaqueous gel is safe for use in the anterior nares. The gel was effective in reducing Staphylococcus aureus nasally, a highly significant hospital-associated pathogen. The gel may be a useful alternative or additive to mupirocin ointment for nasal use prior to surgery, noting that 80% of hospital-associated S. aureus infections are due to the same organism found in the nose. This gel also kills all enveloped viruses tested and should be considered for studies to reduce infection and transmission of coronaviruses and influenza viruses.

Anti-Bacterial Agents/pharmacology , Carrier State/microbiology , Laurates/pharmacology , Monoglycerides/pharmacology , Nasal Cavity/diagnostic imaging , Staphylococcal Infections/drug therapy , Adolescent , Adult , Colony Count, Microbial , Gels/chemistry , Gels/pharmacology , Healthy Volunteers , Humans , Middle Aged , Mupirocin/pharmacology , Nasal Cavity/microbiology , Staphylococcal Infections/microbiology , Staphylococcus aureus/drug effects , Young Adult