Drug Weaponry to Fight Against SARS-CoV-2.
Ontology highlight
ABSTRACT:
SUBMITTER: Cabezon E
PROVIDER: S-EPMC7477106 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The virus responsible for the coronavirus viral pandemic is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging SARS-CoV-2 variants caused by distinctive mutations within the viral spike glycoprotein of SARS-CoV-2 are considered the cause for the rapid spread of the disease and make it challenging to treat SARS-CoV-2. The manufacturing of appropriate efficient vaccines and therapeutics is the only option to combat this pandemic. Nanomedicine has enabled the delivery of nucleic acids and protein-based vaccines to antigen-presenting cells to produce protective immunity against the coronavirus. Nucleic acid-based vaccines, particularly mRNA nanotechnology vaccines, are the best prevention option against the SARS-CoV-2 pandemic worldwide, and they are effective against the novel coronavirus and its multiple variants. This review will report on progress made thus far with SARS-CoV-2 vaccines and beyond employing nanotechnology-based nucleic acid vaccine approaches.
| S-EPMC10175023 | biostudies-literature
Project description:Since 2004, we have been developing nanomaterials with antimicrobial properties, the so-called nanoantimicrobials. When the coronavirus disease 2019 (COVID-19) emerged, we started investigating new and challenging routes to nanoantivirals. The two fields have some important points of contact. We would like to share with the readership our vision of the role a (nano)materials scientist can play in the fight against the COVID-19 pandemic. As researchers specifically working on surfaces and nanomaterials, in this letter we underline the importance of nanomaterial-based technological solutions in several aspects of the fight against the virus. While great resources are understandably being dedicated to treatment and diagnosis, more efforts could be dedicated to limit the virus spread. Increasing the efficacy of personal protection equipment, developing synergistic antiviral coatings, are only two of the cases discussed. This is not the first nor the last pandemic: our nanomaterials community may offer several technological solutions to challenge the ongoing and future global health emergencies. Readers' feedback and suggestions are warmly encouraged.
| S-EPMC7221591 | biostudies-literature
Project description:Here, we propose the molecular hybridization of dihydroartemisinin (DHA) and ursodeoxycholic bile acid (UDCA), approved drugs, for the preparation of antiviral agents against SARS-CoV-2. DHA and UDCA were selected on the basis of their recently demonstrated in vitro activity against SARS-CoV-2. A selection of DHA-UDCA-based hybrids obtained by varying the nature of the linkage and the bile acid conjugation point as well as unconjugated DHA and UDCA were tested in vitro for cytotoxicity and anti-SARS-CoV-2 activity on Vero E6 and Calu-3 human lung cells. The hybrid DHA-t-UDCMe, obtained by conjugation via click chemistry on a gram scale, was identified as a potential candidate for SARS-CoV-2 infection treatment due to significant reduction of viral replication, possibly involving ACE2 downregulation, no cytotoxicity, and chemical stability.
| S-EPMC10688034 | biostudies-literature
Project description:The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is having serious consequences on health and the economy worldwide. All evidence-based treatment strategies need to be considered to combat this new virus. Drugs need to be considered on scientific grounds of efficacy, safety and cost. Chloroquine (CQ) and hydroxychloroquine (HCQ) are old drugs used in the treatment of malaria. Moreover, their antiviral properties have been previously studied, including against coronaviruses, where evidence of efficacy has been found. In the current race against time triggered by the COVID-19 pandemic, the search for new antivirals is very important. However, consideration should be given to old drugs with known anti-coronavirus activity, such as CQ and HCQ. These could be integrated into current treatment strategies while novel treatments are awaited, also in light of the fact that they display an anticoagulant effect that facilitates the activity of low-molecular-weight heparin, aimed at preventing acute respiratory distress syndrome (ARDS)-associated thrombotic events. The safety of CQ and HCQ has been studied for over 50 years, however recently published data raise concerns for cardiac toxicity of CQ/HCQ in patients with COVID-19. This review also re-examines the real information provided by some of the published alarming reports, although concluding that cardiac toxicity should in any case be stringently monitored in patients receiving CQ/HCQ.
| S-EPMC7334645 | biostudies-literature
Project description:Since the beginning of the COVID-19 pandemic, large in silico screening studies and numerous in vitro studies have assessed the antiviral activity of various drugs on SARS-CoV-2. In the context of health emergency, drug repurposing represents the most relevant strategy because of the reduced time for approval by international medicines agencies, the low cost of development and the well-known toxicity profile of such drugs. Herein, we aim to review drugs with in vitro antiviral activity against SARS-CoV-2, combined with molecular docking data and results from preliminary clinical studies. Finally, when considering all these previous findings, as well as the possibility of oral administration, 11 molecules consisting of nelfinavir, favipiravir, azithromycin, clofoctol, clofazimine, ivermectin, nitazoxanide, amodiaquine, heparin, chloroquine and hydroxychloroquine, show an interesting antiviral activity that could be exploited as possible drug candidates for COVID-19 treatment.
| S-EPMC8579950 | biostudies-literature
Project description:The outbreak of a new coronavirus (SARS-CoV-2), which is responsible for the COVID-19 disease and is spreading rapidly around the world, urgently requires effective therapeutic treatments. In this context, drug repurposing represents a valuable strategy, as it enables accelerating the identification of drug candidates with already known safety profiles, possibly aiding in the late stages of clinical evaluation. Moreover, therapeutic treatments based on drugs with beneficial multi-target activities (polypharmacology) may show an increased antiviral activity or help to counteract severe complications concurrently affecting COVID-19 patients. In this study, we present the results of a computational drug repurposing campaign that aimed at identifying potential inhibitors of the main protease (Mpro) of the SARS-CoV-2. The performed in silico screening allowed the identification of 22 candidates with putative SARS-CoV-2 Mpro inhibitory activity. Interestingly, some of the identified compounds have recently entered clinical trials for COVID-19 treatment, albeit not being assayed for their SARS-CoV-2 antiviral activity. Some candidates present a polypharmacology profile that may be beneficial for COVID-19 treatment and, to the best of our knowledge, have never been considered in clinical trials. For each repurposed compound, its therapeutic relevance and potential beneficial polypharmacological effects that may arise due to its original therapeutic indication are thoroughly discussed.
| S-EPMC7938350 | biostudies-literature
Project description:The newly emerged SARS-CoV-2 strains from the coronavirus (CoV) family is causing one of the most disruptive pandemics of the past century. Developing antiviral drugs is a challenge for the scientific community and pharmaceutical industry. Given the health emergency, repurposing of existing antiviral, antiinflammatory or antimalarial drugs is an attractive option for controlling SARS-CoV-2 with drugs. However, phytochemicals selected based on ethnomedicinal information as well as in vitro antiviral studies could be promising as well. Here, we summarise the phytochemicals with reported anti-CoV activity, and further analyzed them computationally to accelerate validation for drug development against SARS-CoV-2. This systematic review started from the most potent phytocompounds (IC50 in μM) against SARS-CoV, followed by a cluster analysis to locate the most suitable lead(s). The advanced molecular docking used the crystallography structure of SARS-CoV-2-cysteine-like protease (SARS-CoV-2-3CLpro) as a target. In total, seventy-eight phytochemicals with anti-CoV activity against different strains in cellular assays, were selected for this computational study, and compared with two existing repurposed FDA-approved drugs: lopinavir and ritonavir. This review brings insights in the potential application of phytochemicals and their derivatives, which could guide researchers to develop safe drugs against SARS-CoV-2.
| S-EPMC7726715 | biostudies-literature
Project description:A novel severe acute respiratory syndrome human coronavirus (SARS HCoV) was identified from respiratory illness patients (named SARS-CoV-2 by ICTV) in December 2019 and has recently emerged as a serious threat to world public health. However, no approved drugs have been found to effectively inhibit the virus. Since it has been reported that HIV protease inhibitors can be used as anti-SARS drugs by targeting SARS-CoV-1 3CLpro, we chose six approved anti-HIV drugs and investigated their binding interactions with 3CLpro to evaluate their potential to become clinical drugs for the new coronavirus pneumonia (COVID-19) caused by SARS-CoV-2 infection. The molecular docking results indicate that the 3CLpro of SARS-CoV-2 has a higher binding affinity for all the studied inhibitors than does SARS-CoV-1. Two docking complexes (indinavir and darunavir) with high docking scores were further subjected to MM-PBSA binding free energy calculations to detail the molecular interactions between these two protease inhibitors and SARS HCoV 3CLpro. Our results show that, among the inhibitors tested, darunavir has the highest binding affinity with SARS-CoV-2 and SARS-CoV-1 3CLpro, indicating that it may have the potential to be used as an anti-COVID-19 clinical drug. The mechanism behind the increased binding affinity of HIV protease inhibitors toward SARS-CoV-2 3CLpro (as compared to SARS-CoV-1) was investigated by MD simulations. Our study provides insight into the possible role of structural flexibility during interactions between SARS HCoV 3CLpro and inhibitors and sheds light on structure-based design of anti-COVID-19 drugs targeting SARS-CoV-2 3CLpro.
| S-EPMC9052367 | biostudies-literature
Project description:The current state of the COVID-19 pandemic is a global health crisis. To fight the novel coronavirus, one of the best-known ways is to block enzymes essential for virus replication. Currently, we know that the SARS-CoV-2 virus encodes about 29 proteins such as spike protein, 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), Papain-like protease (PLpro), and nucleocapsid (N) protein. SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) for viral entry and transmembrane serine protease family member II (TMPRSS2) for spike protein priming. Thus in order to speed up the discovery of potential drugs, we develop DockCoV2, a drug database for SARS-CoV-2. DockCoV2 focuses on predicting the binding affinity of FDA-approved and Taiwan National Health Insurance (NHI) drugs with the seven proteins mentioned above. This database contains a total of 3,109 drugs. DockCoV2 is easy to use and search against, is well cross-linked to external databases, and provides the state-of-the-art prediction results in one site. Users can download their drug-protein docking data of interest and examine additional drug-related information on DockCoV2. Furthermore, DockCoV2 provides experimental information to help users understand which drugs have already been reported to be effective against MERS or SARS-CoV. DockCoV2 is available at https://covirus.cc/drugs/.
| S-EPMC7778986 | biostudies-literature
Project description:BackgroundThe recent emergence of COVID-19 has caused an immense global public health crisis. The etiological agent of COVID-19 is the novel coronavirus SARS-CoV-2. More research in the field of developing effective vaccines against this emergent viral disease is indeed a need of the hour.ObjectiveThe aim of this study was to identify effective vaccine candidates that can offer a new milestone in the battle against COVID-19.MethodsWe used a reverse vaccinology approach to explore the SARS-CoV-2 genome among strains prominent in India. Epitopes were predicted and then molecular docking and simulation were used to verify the molecular interaction of the candidate antigenic peptide with corresponding amino acid residues of the host protein.ResultsA promising antigenic peptide, GVYFASTEK, from the surface glycoprotein of SARS-CoV-2 (protein accession number QIA98583.1) was predicted to interact with the human major histocompatibility complex (MHC) class I human leukocyte antigen (HLA)-A*11-01 allele, showing up to 90% conservancy and a high antigenicity value. After vigorous analysis, this peptide was predicted to be a suitable epitope capable of inducing a strong cell-mediated immune response against SARS-CoV-2.ConclusionsThese results could facilitate selecting SARS-CoV-2 epitopes for vaccine production pipelines in the immediate future. This novel research will certainly pave the way for a fast, reliable, and effective platform to provide a timely countermeasure against this dangerous virus responsible for the COVID-19 pandemic.
| S-EPMC9048139 | biostudies-literature