Metal Complexes as Antiviral Agents for SARS-CoV-2.
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ABSTRACT:
SUBMITTER: Karges J
PROVIDER: S-EPMC8239769 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:SARS-CoV-2 emerged in 2019 as a devastating viral pathogen with no available preventative or treatment to control what led to the current global pandemic. The continued spread of the virus and increasing death toll necessitate the development of effective antiviral treatments to combat this virus. To this end, we evaluated a new class of organometallic complexes as potential antivirals. Our findings demonstrate that two pentamethylcyclopentadienyl (Cp*) rhodium piano stool complexes, Cp*Rh(1,3-dicyclohexylimidazol-2-ylidene)Cl2 (complex 2) and Cp*Rh(dipivaloylmethanato)Cl (complex 4), have direct virucidal activity against SARS-CoV-2. Subsequent in vitro testing suggests that complex 4 is the more stable and effective complex and demonstrates that both 2 and 4 have low toxicity in Vero E6 and Calu-3 cells. The results presented here highlight the potential application of organometallic complexes as antivirals and support further investigation into their activity.
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Project description:The COVID-19 pandemic has claimed more than a million lives worldwide within a short time span. Due to the unavailability of specific antiviral drugs or vaccine, the infections are causing panic both in general public and among healthcare providers. Therefore, an urgent discovery and development of effective antiviral drug for the treatment of COVID-19 is highly desired. Targeting the main protease (Mpro) of the causative agent, SARS-CoV-2 has great potential for drug discovery and drug repurposing efforts. Published crystal structures of SARS-CoV-2 Mpro further facilitated in silico investigations for discovering new inhibitors against Mpro. The present study aimed to screen several libraries of synthetic flavonoids and benzisothiazolinones as potential SARS-CoV-2 Mpro inhibitors using in silico methods. The short-listed compounds after virtual screening were filtered through SwissADME modeling tool to remove molecules with unfavorable pharmacokinetics and medicinal properties. The drug-like molecules were further subjected to iterative docking for the identification of top binders of SARS-CoV-2 Mpro. Finally, molecular dynamic (MD) simulations and binding free energy calculations were performed for the evaluation of the dynamic behavior, stability of protein-ligand complex, and binding affinity, resulting in the identification of thioflavonol, TF-9 as a potential inhibitor of Mpro. The computational studies further revealed the binding of TF-9 close to catalytic dyad and interactions with conserved residues in the S1 subsite of the substrate binding site. Our in-silico study demonstrated that synthetic analogs of flavonoids, particularly thioflavonols, have a strong tendency to inhibit the main protease Mpro, and thereby inhibit the reproduction of SARS-CoV-2. Communicated by Ramaswamy H. Sarma.
| S-EPMC7754928 | biostudies-literature
Project description:The recent pandemic of COVID-19 has raised global health concerns. Preventing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) activity in the body is a very promising method to overcome the COVID-19 pandemic. One of the prevention methods is constraining the binding process among the human cell receptor-ACE2 and coronavirus spike protein. In the research done, the effect of deformation of the spike protein structure, due to the covalent organic frameworks (COFs), in reducing the interactions of ACE2 and the spike protein by the computational method was investigated. In this regard, atomic analysis of the interactions of ACE2 and the spike protein is provided using a molecular dynamics simulation. First, we investigated the interactions of the three different COFs, including COF-78, DAAQ-TFP, and COF-OEt, with the spike protein by analyzing the bond energies, as well as structural changes of the spike protein. Then, intermolecular interactions of the deformed spike protein along with ACE2 were assessed to clarify the protein's fusion after the deformation. As indicated by the results, although all introduced COFs deformed the spike protein in an effective way, COF-78 showed the best performance in the prevention of spike protein-ACE2 interactions by changing the molecular structure of the protein. Indeed, the interaction analysis of the deformed spike protein by COF-78 with the ACE2 showed that their interactions had the lowest absolute value of energy, along with the least amount of hydrogen bonds, in which the compaction of the protein was lower compared to the other deformed proteins. Moreover, having a high contact area with an aqueous media as well as severe fluctuations during the simulation time confirmed the positive performance of COF-78. In the current study, we aimed to introduce novel materials and COVID-19 prevention methodology that can be used in face masks and for surface disinfection.
| S-EPMC8550915 | biostudies-literature
Project description: Not available
| S-EPMC8929374 | biostudies-literature
Project description:The pandemic of COVID-19 has an unprecedented impact on global health and economy. The novel SARS-CoV-2 is recognized as the etiological agent of current outbreak. Because of its contagious human-to-human transmission, it is an utmost global health emergency at present. To mitigate this threat many scientists and researchers are racing to develop antiviral therapy against the virus. Unfortunately, to date no vaccine or antiviral therapeutic is approved thus there is an urgent need to discover antiviral agent to help the individual who are at high risk. Virus main protease or chymotrypsin-like protease plays a pivotal role in virus replication and transcription; thus, it is considered as an attractive drug target to combat the COVID-19. In this study, multistep structure based virtual screening of CAS antiviral database is performed for the identification of potent and effective small molecule inhibitors against chymotrypsin-like protease of SARS-CoV-2. Consensus scoring strategy combine with flexible docking is used to extract potential hits. As a result of extensive virtual screening, 4 hits were shortlisted for MD simulation to study their stability and dynamic behavior. Insight binding modes demonstrated that the selected hits stabilized inside the binding pocket of the target protein and exhibit complementarity with the active site residues. Our study provides compounds for further in vitro and in vivo studies against SARS-CoV-2.
| S-EPMC7817485 | biostudies-literature
Project description:We synthesized a set of small molecules using a molecular hybridization approach with good yields. The antiviral properties of the synthesized conjugates against the SAR-CoV-2 virus were investigated and their cytotoxicity was also determined. Among all the synthesized conjugates, compound 9f showed potential against SARS-CoV-2 and low cytotoxicity. The conjugates' selectivity indexes (SIs) were determined to correlate the antiviral properties and cytotoxicity. The observed biological data were further validated using computational studies.
| S-EPMC9501548 | biostudies-literature
Project description:IntroductionThe coronavirus disease 2019 (COVID-19) pandemic has demonstrated the need for novel, affordable, and efficient reagents to help reduce viral transmission, especially in high-risk environments including medical treatment facilities, close quarters, and austere settings. We examined transition-metal nanozeolite suspensions and quaternary ammonium compounds as an antiviral surface coating for various textile materials.MethodsZeolites are crystalline porous aluminosilicate materials, with the ability of ion-exchanging different cations. Nanozeolites (30 nm) were synthesized and then ion-exchanged with silver, zinc and copper ions. Benzalkonium nitrate (BZN) was examined as the quaternary ammonium ion (quat). Suspensions of these materials were tested for antiviral activity towards SARS-CoV-2 using plaque assay and immunostaining. Suspensions of the nanozeolite and quat were deposited on polyester and cotton fabrics and the ability of these textiles towards neutralizing SARS-CoV-2 was examined.ResultsWe hypothesized that transition metal ion containing zeolites, particularly silver and zinc (AM30) and silver and copper (AV30), would be effective in reducing the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Additionally, AM30 and AV30 antiviral potency was tested when combined with a quaternary ammonium carrier, BZN. Our results indicate that exposure of SARS-CoV-2 to AM30 and/or AV30 suspensions reduced viral loads with time and exhibited dose-dependence. Antiviral activities of the combination of zeolite and BZN compositions were significantly enhanced. When used in textiles, AM30 and AV30-coated cotton and polyester fabrics alone or in combination with BZN exhibited significant antiviral properties, which were maintained even after various stress tests, including washes, SARS-CoV-2-repeated exposures, or treatments with soil-like materials.ConclusionThis study shows the efficacy of transition metal nanozeolite formulations as novel antiviral agents and establishes that nanozeolite with silver and zinc ions (AM30) and nanozeolite with silver and copper ions (AV30) when combined with benzalkonium nitrate (BZN) quickly and continuously inactivate SARS-CoV-2 in suspension and on fabric materials.
| S-EPMC10164392 | biostudies-literature
Project description:Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS-CoV-2 pandemic. Nirmatrelvir - an orally available inhibitor of the 3-chymotrypsin-like cysteine protease - has been shown to reduce the risk of progression to severe COVID-19. However, the impact of nirmatrelvir treatment on the development of SARS-CoV-2-specific adaptive immune responses is unknown. Here, by using mouse models of SARS-CoV-2 infection, we show that nirmatrelvir administration blunts the development of SARS-CoV-2-specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir-treated mice recruited significantly fewer memory T and B cells to the infected lungs and to mediastinal lymph nodes, respectively. Together, the data highlight a potential negative impact of nirmatrelvir treatment with important implications for clinical management and might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals.
| S-SCDT-10_15252-EMMM_202317580 | biostudies-other
Project description:This study aimed to evaluate the pharmacological and toxicological potential of five known antiviral agents and their derivatives through computational modeling. Ritonavir, remdesivir, chloroquine, lopinavir, lieckol, and their derivatives were subjected to molecular docking analysis against five SARS-CoV-2 target proteins. The absorption, distribution, metabolism, excretion, and toxicity properties of the compounds with high affinity for the SARS-CoV-2 target proteins were predicted. Dieckol demonstrated the highest binding affinity for all the SARS-CoV-2 target proteins, while lopinavir and ritonavir showed a relatively high-binding affinity for 3-chymotrypsin-like protease, main protease, and RNA-dependent RNA polymerase. The compounds fulfilled the Lipinski rule, possess moderate water solubility, gastrointestinal absorption absorption, bioavailability, synthetic accessibility, and optimum lipophilicity. Hence, this study proves the therapeutic potential of dieckol, lopinavir, and ritonavir.
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