Saquinavir for COVID-19
Saquinavir has been reported as potentially beneficial for treatment of COVID-19. We have not reviewed these studies. See all other treatments.
Recent advances in chemometric modelling of inhibitors against SARS-CoV-2, Heliyon, doi:10.1016/j.heliyon.2024.e24209 ,
Identification of FDA Approved Drugs Targeting COVID-19 Virus by Structure-Based Drug Repositioning, American Chemical Society (ACS), doi:10.26434/chemrxiv.12003930.v1 ,
The new strain of Coronaviruses (SARS-CoV-2), and the resulting Covid-19 disease has spread swiftly across the globe after its initial detection in late December 2019 in Wuhan, China, resulting in a pandemic status declaration by WHO within 3 months. Given the heavy toll of this pandemic, researchers are actively testing various strategies including new and repurposed drugs as well as vaccines. In the current brief report, we adopted a repositioning approach using insilico molecular modeling screening using FDA approved drugs with established safety profiles for potential inhibitory effects on Covid-19 virus. We started with structure based drug design by screening more than 2000 FDA approved drugsagainst Covid-19 virus main protease enzyme (Mpro) substrate-binding pocket to identify potential hits based on their binding energies, binding modes, interacting amino acids, and therapeutic indications. In addition, we elucidate preliminary pharmacophore features for candidates bound to Covid-19 virus Mpro substratebinding pocket. The top hits include anti-viral drugs such as Darunavir, Nelfinavirand Saquinavir, some of which are already being tested in Covid-19 patients. Interestingly, one of the most promising hits in our screen is the hypercholesterolemia drug Rosuvastatin. These results certainly do not confirm or indicate antiviral activity, but can rather be used as a starting point for further in vitro and in vivo testing, either individually or in combination.
Fast Identification of Possible Drug Treatment of Coronavirus Disease-19 (COVID-19) through Computational Drug Repurposing Study, Journal of Chemical Information and Modeling, doi:10.1021/acs.jcim.0c00179 ,
Identification of chymotrypsin-like protease inhibitors of SARS-CoV-2 via integrated computational approach, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2020.1751298 ,
In silico studies on therapeutic agents for COVID-19: Drug repurposing approach, Life Sciences, doi:10.1016/j.lfs.2020.117652 ,
Repurposing Therapeutics for COVID-19: Rapid Prediction of Commercially available drugs through Machine Learning and Docking, medRxiv, doi:10.1101/2020.04.05.20054254 ,
ABSTRACTBackgroundThe outbreak of the novel coronavirus disease COVID-19, caused by the SARS-CoV-2 virus has spread rapidly around the globe during the past 3 months. As the virus infected cases and mortality rate of this disease is increasing exponentially, scientists and researchers all over the world are relentlessly working to understand this new virus along with possible treatment regimens by discovering active therapeutic agents and vaccines. So, there is an urgent requirement of new and effective medications that can treat the disease caused by SARS-CoV-2.Methods and findingsWe perform the study of drugs that are already available in the market and being used for other diseases to accelerate clinical recovery, in other words repurposing of existing drugs. The vast complexity in drug design and protocols regarding clinical trials often prohibit developing various new drug combinations for this epidemic disease in a limited time. Recently, remarkable improvements in computational power coupled with advancements in Machine Learning (ML) technology have been utilized to revolutionize the drug development process. Consequently, a detailed study using ML for the repurposing of therapeutic agents is urgently required. Here, we report the ML model based on the Naïve Bayes algorithm, which has an accuracy of around 73% to predict the drugs that could be used for the treatment of COVID-19. Our study predicts around ten FDA approved commercial drugs that can be used for repurposing. Among all, we suggest that the antiretroviral drug Atazanavir (DrugBank ID – DB01072) would probably be one of the most effective drugs based on the selected criterions.ConclusionsOur study can help clinical scientists in being more selective in identifying and testing the therapeutic agents for COVID-19 treatment. The ML based approach for drug discovery as reported here can be a futuristic smart drug designing strategy for community applications.Author summaryWhy was this study done?The recent outbreak of novel coronavirus disease (COVID-19) is now considered to be a pandemic threat to the global population. The new coronavirus, 2019-nCoV has now affected more than 200 countries with over 17,83,941 cases confirmed and 1,09,312 deaths reported all over the world [as on 12 April 2020].There is an urgent need for the development of drugs or vaccine which can save people worldwide. However, the vast complexity in drug design and protocols regarding clinical trials often prohibit developing various new drug combinations for this epidemic disease. Recently, Artificial Intelligence (AI) technology have been utilized to revolutionize the drug development process. Can we use AI based repurposing of existing drugs for accelerated clinical trial in the treatment of COVID-19?What did the researchers do and find?Here, we report the Machine Learning (ML) model based on the Naïve Bayes algorithm, which has an accuracy of around 73% to predict the drugs that could be used for the..
Identification of potential molecules against COVID-19 main protease through structure-guided virtual screening approach, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2020.1768151 ,
Using integrated computational approaches to identify safe and rapid treatment for SARS-CoV-2, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2020.1764392 ,
Discovery of potential multi-target-directed ligands by targeting host-specific SARS-CoV-2 structurally conserved main protease, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2020.1760137 ,
Transcriptome-based drug repositioning for coronavirus disease 2019 (COVID-19), Pathogens and Disease, doi:10.1093/femspd/ftaa036 ,
ABSTRACT The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world has led to a pandemic with high morbidity and mortality. However, there are no effective drugs to prevent and treat the disease. Transcriptome-based drug repositioning, identifying new indications for old drugs, is a powerful tool for drug development. Using bronchoalveolar lavage fluid transcriptome data of COVID-19 patients, we found that the endocytosis and lysosome pathways are highly involved in the disease and that the regulation of genes involved in neutrophil degranulation was disrupted, suggesting an intense battle between SARS-CoV-2 and humans. Furthermore, we implemented a coexpression drug repositioning analysis, cogena, and identified two antiviral drugs (saquinavir and ribavirin) and several other candidate drugs (such as dinoprost, dipivefrine, dexamethasone and (-)-isoprenaline). Notably, the two antiviral drugs have also previously been identified using molecular docking methods, and ribavirin is a recommended drug in the diagnosis and treatment protocol for COVID pneumonia (trial version 5–7) published by the National Health Commission of the P.R. of China. Our study demonstrates the value of the cogena-based drug repositioning method for emerging infectious diseases, improves our understanding of SARS-CoV-2-induced disease, and provides potential drugs for the prevention and treatment of COVID-19 pneumonia.
A review on in silico virtual screening methods in COVID-19 using anticancer drugs and other natural/chemical inhibitors, Exploration of Targeted Anti-tumor Therapy, doi:10.37349/etat.2023.00177 ,
The present coronavirus disease 2019 (COVID-19) pandemic scenario has posed a difficulty for cancer treatment. Even under ideal conditions, malignancies like small cell lung cancer (SCLC) are challenging to treat because of their fast development and early metastases. The treatment of these patients must not be jeopardized, and they must be protected as much as possible from the continuous spread of the COVID-19 infection. Initially identified in December 2019 in Wuhan, China, the contagious coronavirus illness 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Finding inhibitors against the druggable targets of SARS-CoV-2 has been a significant focus of research efforts across the globe. The primary motivation for using molecular modeling tools against SARS-CoV-2 was to identify candidates for use as therapeutic targets from a pharmacological database. In the published study, scientists used a combination of medication repurposing and virtual drug screening methodologies to target many structures of SARS-CoV-2. This virus plays an essential part in the maturation and replication of other viruses. In addition, the total binding free energy and molecular dynamics (MD) modeling findings showed that the dynamics of various medications and substances were stable; some of them have been tested experimentally against SARS-CoV-2. Different virtual screening (VS) methods have been discussed as potential means by which the evaluated medications that show strong binding to the active site might be repurposed for use against SARS-CoV-2.
Virtual high-throughput screening: Potential inhibitors targeting aminopeptidase N (CD13) and PIKfyve for SARS-CoV-2, Open Life Sciences, doi:10.1515/biol-2022-0637 ,
Abstract Since the outbreak of the novel coronavirus nearly 3 years ago, the world’s public health has been under constant threat. At the same time, people’s travel and social interaction have also been greatly affected. The study focused on the potential host targets of SARS-CoV-2, CD13, and PIKfyve, which may be involved in viral infection and the viral/cell membrane fusion stage of SARS-CoV-2 in humans. In this study, electronic virtual high-throughput screening for CD13 and PIKfyve was conducted using Food and Drug Administration-approved compounds in ZINC database. The results showed that dihydroergotamine, Saquinavir, Olysio, Raltegravir, and Ecteinascidin had inhibitory effects on CD13. Dihydroergotamine, Sitagliptin, Olysio, Grazoprevir, and Saquinavir could inhibit PIKfyve. After 50 ns of molecular dynamics simulation, seven compounds showed stability at the active site of the target protein. Hydrogen bonds and van der Waals forces were formed with target proteins. At the same time, the seven compounds showed good binding free energy after binding to the target proteins, providing potential drug candidates for the treatment and prevention of SARS-CoV-2 and SARS-CoV-2 variants.
Converging Paths: A Comprehensive Review of the Synergistic Approach between Complementary Medicines and Western Medicine in Addressing COVID-19 in 2020, BioMed, doi:10.3390/biomed3020025 ,
The rapid spread of the new coronavirus disease (COVID-19) caused by SARS-CoV-2 has become a global pandemic. Although specific vaccines are available and natural drugs are being researched, supportive care and specific treatments to alleviate symptoms and improve patient quality of life remain critical. Chinese medicine (CM) has been employed in China due to the similarities between the epidemiology, genomics, and pathogenesis of SARS-CoV-2 and SARS-CoV. Moreover, the integration of other traditional oriental medical systems into the broader framework of integrative medicine can offer a powerful approach to managing the disease. Additionally, it has been reported that integrated medicine has better effects and does not increase adverse drug reactions in the context of COVID-19. This article examines preventive measures, potential infection mechanisms, and immune responses in Western medicine (WM), as well as the pathophysiology based on principles of complementary medicine (CM). The convergence between WM and CM approaches, such as the importance of maintaining a strong immune system and promoting preventive care measures, is also addressed. Current treatment options, traditional therapies, and classical prescriptions based on empirical knowledge are also explored, with individual patient circumstances taken into account. An analysis of the potential benefits and challenges associated with the integration of complementary and Western medicine (WM) in the treatment of COVID-19 can provide valuable guidance, enrichment, and empowerment for future research endeavors.
In Silico Screening of Drugs That Target Different Forms of E Protein for Potential Treatment of COVID-19, Pharmaceuticals, doi:10.3390/ph16020296 ,
Recently the E protein of SARS-CoV-2 has become a very important target in the potential treatment of COVID-19 since it is known to regulate different stages of the viral cycle. There is biochemical evidence that E protein exists in two forms, as monomer and homopentamer. An in silico screening analysis was carried out employing 5852 ligands (from Zinc databases), and performing an ADMET analysis, remaining a set of 2155 compounds. Furthermore, docking analysis was performed on specific sites and different forms of the E protein. From this study we could identify that the following ligands showed the highest binding affinity: nilotinib, dutasteride, irinotecan, saquinavir and alectinib. We carried out some molecular dynamics simulations and free energy MM–PBSA calculations of the protein–ligand complexes (with the mentioned ligands). Of worthy interest is that saquinavir, nilotinib and alectinib are also considered as a promising multitarget ligand because it seems to inhibit three targets, which play an important role in the viral cycle. On the other side, saquinavir was shown to be able to bind to E protein both in its monomeric as well as pentameric forms. Finally, further experimental assays are needed to probe our hypothesis derived from in silico studies.
In silico identification of drug candidates against COVID-19, Informatics in Medicine Unlocked, doi:10.1016/j.imu.2020.100461 ,
Polyphenols as alternative treatments of COVID-19, Computational and Structural Biotechnology Journal, doi:10.1016/j.csbj.2021.09.022 ,
Identification of potential Mpro inhibitors for the treatment of COVID-19 by using systematic virtual screening approach, Molecular Diversity, doi:10.1007/s11030-020-10130-1 ,
Virtual screening of quinoline derived library for SARS-COV-2 targeting viral entry and replication, Journal of Biomolecular Structure and Dynamics, doi:10.1080/07391102.2021.1913228 ,
Novel Drug Design for Treatment of COVID-19: A Systematic Review of Preclinical Studies, Canadian Journal of Infectious Diseases and Medical Microbiology, doi:10.1155/2022/2044282 ,
Background. Since the beginning of the novel coronavirus (SARS-CoV-2) disease outbreak, there has been an increasing interest in discovering potential therapeutic agents for this disease. In this regard, we conducted a systematic review through an overview of drug development (in silico, in vitro, and in vivo) for treating COVID-19. Methods. A systematic search was carried out in major databases including PubMed, Web of Science, Scopus, EMBASE, and Google Scholar from December 2019 to March 2021. A combination of the following terms was used: coronavirus, COVID-19, SARS-CoV-2, drug design, drug development, In silico, In vitro, and In vivo. A narrative synthesis was performed as a qualitative method for the data synthesis of each outcome measure. Results. A total of 2168 articles were identified through searching databases. Finally, 315 studies (266 in silico, 34 in vitro, and 15 in vivo) were included. In studies with in silico approach, 98 article study repurposed drug and 91 studies evaluated herbal medicine on COVID-19. Among 260 drugs repurposed by the computational method, the best results were observed with saquinavir (n = 9), ritonavir (n = 8), and lopinavir (n = 6). Main protease (n = 154) following spike glycoprotein (n = 62) and other nonstructural protein of virus (n = 45) was among the most studied targets. Doxycycline, chlorpromazine, azithromycin, heparin, bepridil, and glycyrrhizic acid showed both in silico and in vitro inhibitory effects against SARS-CoV-2. Conclusion. The preclinical studies of novel drug design for COVID-19 focused on main protease and spike glycoprotein as targets for antiviral development. From evaluated structures, saquinavir, ritonavir, eucalyptus, Tinospora cordifolia, aloe, green tea, curcumin, pyrazole, and triazole derivatives in in silico studies and doxycycline, chlorpromazine, and heparin from in vitro and human monoclonal antibodies from in vivo studies showed promised results regarding efficacy. It seems that due to the nature of COVID-19 disease, finding some drugs with multitarget antiviral actions and anti-inflammatory potential is valuable and some herbal medicines have this potential.
Molecular Docking and Virtual Screening Based Prediction of Drugs for COVID-19, Combinatorial Chemistry & High Throughput Screening, doi:10.2174/1386207323666200814132149 ,
Aims: To predict potential drugs for COVID-19 by using molecular docking for virtual screening of drugs approved for other clinical applications. Background: SARS-CoV-2 is the betacoronavirus responsible for the COVID-19 pandemic. It was listed as a potential global health threat by the WHO due to high mortality, high basic reproduction number, and lack of clinically approved drugs and vaccines. The genome of the virus responsible for COVID-19 has been sequenced. In addition, the three-dimensional structure of the main protease has been determined experimentally. Objective: To identify potential drugs that can be repurposed for treatment of COVID-19 by using molecular docking based virtual screening of all approved drugs. Methods: A list of drugs approved for clinical use was obtained from the SuperDRUG2 database. The structure of the target in the apo form, as well as structures of several target-ligand complexes, were obtained from RCSB PDB. The structure of SARS-CoV-2 Mpro determined from X-ray diffraction data was used as the target. Data regarding drugs in clinical trials for COVID-19 was obtained from clinicaltrials.org. Input for molecular docking based virtual screening was prepared by using Obabel and customized python, bash, and awk scripts. Molecular docking calculations were carried out with Vina and SMINA, and the docked conformations were analyzed and visualized with PLIP, Pymol, and Rasmol. Results: Among the drugs that are being tested in clinical trials for COVID-19, Danoprevir and Darunavir were predicted to have the highest binding affinity for the Main protease (Mpro) target of SARS-CoV-2. Saquinavir and Beclabuvir were identified as the best novel candidates for COVID-19 therapy by using Virtual Screening of drugs approved for other clinical indications. Conclusion: Protease inhibitors approved for treatment of other viral diseases have the potential to be repurposed for treatment of COVID-19.
Potential inhibitors of SARS-CoV-2: recent advances, Journal of Drug Targeting, doi:10.1080/1061186X.2020.1853736 ,
Virtual Screening of Substances Used in the Treatment of SARS-CoV-2 Infection and Analysis of Compounds With Known Action on Structurally Similar Proteins From Other Viruses, Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2022.113432 ,
Antivirals for COVID-19: A critical review, Clinical Epidemiology and Global Health, doi:10.1016/j.cegh.2020.07.006 ,
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