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1.
Int J Mol Sci ; 23(5)2022 Feb 27.
Article in English | MEDLINE | ID: covidwho-1715407

ABSTRACT

The overall impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on our society is unprecedented. The identification of small natural ligands that could prevent the entry and/or replication of the coronavirus remains a pertinent approach to fight the coronavirus disease (COVID-19) pandemic. Previously, we showed that the phenolic compounds corilagin and 1,3,6-tri-O-galloyl-ß-D-glucose (TGG) inhibit the interaction between the SARS-CoV-2 spike protein receptor binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 target receptor on the cell membrane of the host organism. Building on these promising results, we now assess the effects of these phenolic ligands on two other crucial targets involved in SARS-CoV-2 cell entry and replication, respectively: transmembrane protease serine 2 (TMPRSS2) and 3-chymotrypsin like protease (3CLpro) inhibitors. Since corilagin, TGG, and tannic acid (TA) share many physicochemical and structural properties, we investigate the binding of TA to these targets. In this work, a combination of experimental methods (biochemical inhibition assays, surface plasmon resonance, and quartz crystal microbalance with dissipation monitoring) confirms the potential role of TA in the prevention of SARS-CoV-2 infectivity through the inhibition of extracellular RBD/ACE2 interactions and TMPRSS2 and 3CLpro activity. Moreover, molecular docking prediction followed by dynamic simulation and molecular mechanics Poisson-Boltzmann surface area (MMPBSA) free energy calculation also shows that TA binds to RBD, TMPRSS2, and 3CLpro with higher affinities than TGG and corilagin. Overall, these results suggest that naturally occurring TA is a promising candidate to prevent and inhibit the infectivity of SARS-CoV-2.


Subject(s)
COVID-19/metabolism , Molecular Docking Simulation , SARS-CoV-2/metabolism , Serine Endopeptidases/metabolism , Tannins/pharmacology , Algorithms , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/epidemiology , COVID-19/virology , Coronavirus 3C Proteases , Glucosides/chemistry , Glucosides/metabolism , Glucosides/pharmacology , Humans , Hydrolyzable Tannins/chemistry , Hydrolyzable Tannins/metabolism , Hydrolyzable Tannins/pharmacology , Kinetics , Pandemics/prevention & control , Protein Binding/drug effects , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism , Surface Plasmon Resonance , Tannins/chemistry , Tannins/metabolism , Virus Internalization/drug effects
2.
J Hazard Mater ; 426: 128070, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1561761

ABSTRACT

In the present contribution, two nationwide surveys of personal protective equipment (PPE) pollution were conducted in Peru and Argentina aiming to provide valuable information regarding the abundance and distribution of PPE in coastal sites. Additionally, PPE items were recovered from the environment and analyzed by Fourier transformed infrared (FTIR) spectroscopy, Scanning electron microscopy (SEM) with Energy dispersive X-ray (EDX), and X-ray diffraction (XRD), and compared to brand-new PPE in order to investigate the chemical and structural degradation of PPE in the environment. PPE density (PPE m-2) found in both countries were comparable to previous studies. FTIR analysis revealed multiple polymer types comprising common PPE, mainly polypropylene, polyamide, polyethylene terephthalate, and polyester. SEM micrographs showed clear weathering signs, such as cracks, cavities, and rough surfaces in face masks and gloves. EDX elemental mapping revealed the presence of elemental additives, such as Ca in gloves and face masks and AgNPs as an antimicrobial agent. Other metals found on the surface of PPE were Mo, P, Ti, and Zn. XRD patterns displayed a notorious decrease in the crystallinity of polypropylene face masks, which could alter its interaction with external contaminants and stability. The next steps in this line of research were discussed.


Subject(s)
COVID-19 , Personal Protective Equipment , Humans , Pandemics , Plastics , SARS-CoV-2
3.
Phys Chem Chem Phys ; 23(27): 14873-14888, 2021 Jul 14.
Article in English | MEDLINE | ID: covidwho-1541260

ABSTRACT

The COVID-19 disease caused by the virus SARS-CoV-2, first detected in December 2019, is still emerging through virus mutations. Although almost under control in some countries due to effective vaccines that are mitigating the worldwide pandemic, the urgency to develop additional vaccines and therapeutic treatments is imperative. In this work, the natural polyphenols corilagin and 1,3,6-tri-O-galloy-ß-d-glucose (TGG) are investigated to determine the structural basis of inhibitor interactions as potential candidates to inhibit SARS-CoV-2 viral entry into target cells. First, the therapeutic potential of the ligands are assessed on the ACE2/wild-type RBD. We first use molecular docking followed by molecular dynamics, to take into account the conformational flexibility that plays a significant role in ligand binding and that cannot be captured using only docking, and then analyze more precisely the affinity of these ligands using MMPBSA binding free energy. We show that both ligands bind to the ACE2/wild-type RBD interface with good affinities which might prevent the ACE2/RBD association. Second, we confirm the potency of these ligands to block the ACE2/RBD association using a combination of surface plasmon resonance and biochemical inhibition assays. These experiments confirm that TGG and, to a lesser extent, corilagin, inhibit the binding of RBD to ACE2. Both experiments and simulations show that the ligands interact preferentially with RBD, while weak binding is observed with ACE2, hence, avoiding potential physiological side-effects induced by the inhibition of ACE2. In addition to the wild-type RBD, we also study numerically three RBD mutations (E484K, N501Y and E484K/N501Y) found in the main SARS-CoV-2 variants of concerns. We find that corilagin could be as effective for RBD/E484K but less effective for the RBD/N501Y and RBD/E484K-N501Y mutants, while TGG strongly binds at relevant locations to all three mutants, demonstrating the significant interest of these molecules as potential inhibitors for variants of SARS-CoV-2.


Subject(s)
Antiviral Agents/chemistry , Gallic Acid/analogs & derivatives , Glucose/analogs & derivatives , Glucosides/chemistry , Hydrolyzable Tannins/chemistry , SARS-CoV-2/drug effects , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Binding Sites , Gallic Acid/chemistry , Glucose/chemistry , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Mutation , Protein Binding/drug effects , Protein Interaction Domains and Motifs/genetics , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Virus Internalization/drug effects
4.
Sci Total Environ ; 798: 149282, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1331225

ABSTRACT

The increasing use of personal protective equipment (PPE) as a sanitary measure against the new coronavirus (SARS-CoV-2) has become a significant source of many environmental risks. The majority of the governments enforce the use of PPE in public areas, such as beaches. Thus, the use and disposal of PPE have compromised most solid waste management strategies, ultimately leading to the occurrence of PPE polluting the marine environment. The present study aimed to monitor the PPE pollution associated with COVID-19 along the coastline of Agadir, Morocco. In parallel, the influence of the activities carried out in each sampled beach before and after the lockdown break was reported. Overall, a total number of 689 PPE items were identified, with a mean density of 1.13 × 10-5 PPE m-2 (0-1.21 × 10-4 PPE m-2). The majority of the PPE items found were face masks (96.81%), out of which 98.4% were surgical masks and 1.6% were reusable cloth masks. The most polluted sites were the beaches with recreational activities, followed by surfing, and fishing as the main activity. Importantly, PPE density increased significantly after lockdown measures. Additionally, the discarded PPE sampled in the supralittoral zone was higher than PPE recorded in the intertidal zone. This confirms that PPE items are driven by the beachgoers during their visit. PPE items are a source of microplastic and chemical pollutants, a substrate to invasive species colonization, and a potential threat of entanglement, ingestion, and/or infection among apex predators. In the specific case of Agadir beaches, significant efforts are required to work on the lack of environmental awareness and education. It is recommended to improve beach cleaning strategies and to penalize incorrect PPE disposal. Additional alternatives may be adopted, as the involvement of biodegradable materials in PPE manufacturing, recycling through pyrolysis, and encouraging reusable and washable masks.


Subject(s)
COVID-19 , Personal Protective Equipment , Communicable Disease Control , Humans , Morocco , Pandemics , Plastics , SARS-CoV-2
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