Ledipasvir for COVID-19

SARS-CoV2 has caused the recent mortal pandemic known as COVID-19. The drug repurposing approach can be employed to find the potential drugs capable of binding SARS-CoV2 structural and nonstructural proteins. The present study aimed to repurpose some common FAD-approved antiviral and non-antiviral drugs computationally for SARS-CoV2 treatment. In the in silico study, 89 FDA-approved drugs and Remdesivir, as the control, were analyzed by molecular docking to inhibit the SARS-CoV2 spike (S) protein as the key player in virus-cell binding. First, the Uniport website was used to find receptor and ganglioside binding domains (RBD and GBD, respectively) of the S protein as the target. The structure of the target was downloaded from RCSB, and 'the ligands' structures were downloaded from PubChem. All structures were refined using SPDV and PyRx software. AutoDock Vina was employed for the docking process. The result showed that 8 drugs, including Ledipasvir, Montelukast, Domperidone, Aprepitant, Folic acid, Losartan, Ticagrelor, and Rivaroxaban, can bind S protein and then inhibit the protein function. In addition, Ledipasvir, Montelukast, and Domperidone can bind GBD of the S protein with higher binding energy (-8.2, -8, -7.9 kcal/mol, respectively). On the other hand, higher RBD binding energy was calculated for Ticagrelor (-6.9 kcal/mol), Folic acid, Montelukast, and Domperidone (-6.5 kcal/mol). Generally, the ligands could inhibit GBD more than RBD. According to the binding energy to S protein and low side effects of the studied medications, Ledipasvir and Losartan can be introduced as the most effective candidates for repurposed drugs. Also, Gly496 and Asn137 are the most engaged amino acids in the ligand-receptor interaction from RBD and GBD, respectively.

Studies on the development of effective and cost-effective oral drugs are the new priority of the pharmaceutical industry for the prevention and treatment of COVID-19. This work was based on the computational analysis of physicochemical parameters, pharmacokinetic and toxicological measurements, molecular docking and in silico measurement of the antiviral activity of 12 repositionable drugs. The Molinspiration platform (physical-chemical parameters), pkCSM® (absorption, distribution, metabolism and excretion), OSIRIS Property Explorer® (toxicological measurements), Seam® (Docking with the RdRp protein) and AVCpred server® (antiviral activity) were used. Considering the 12 selected repositionable drugs, molecular anchoring data with the RdRp protein, only the drug tilorone had lower binding energy than the control used in this study (Molnupiravir). Ledipasvir, daclatasvir and piperaquine showed the best percentage of antiviral inhibition considering the control pattern. ADMETox data showed that piperaquine has a high toxicological potential for mutagenesis, tumorigenesis and irritant effects. The findings of this study indicate that ledipasvir and daclatasvir showed greatest potential for inhibition RdRp and action against COVID-19.

The emergence of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected many countries throughout the world. As urgency is a necessity, most efforts have focused on identifying small molecule drugs that can be repurposed for use as anti-SARS-CoV-2 agents. Although several drug candidates have been identified using in silico method and in vitro studies, most of these drugs require the support of in vivo data before they can be considered for clinical trials. Several drugs are considered promising therapeutic agents for COVID-19. In addition to the direct-acting antiviral drugs, supportive therapies including traditional Chinese medicine, immunotherapies, immunomodulators, and nutritional therapy could contribute a major role in treating COVID-19 patients. Some of these drugs have already been included in the treatment guidelines, recommendations, and standard operating procedures. In this article, we comprehensively review the approved and potential therapeutic drugs, immune cells-based therapies, immunomodulatory agents/drugs, herbs and plant metabolites, nutritional and dietary for COVID-19.

<ns4:p>We prepared the three-dimensional model of the SARS-CoV-2 (aka 2019-nCoV) 3C-like protease (3CL<ns4:sup>pro</ns4:sup>) using the crystal structure of the highly similar (96% identity) ortholog from the SARS-CoV. All residues involved in the catalysis, substrate binding and dimerisation are 100% conserved. Comparison of the polyprotein PP1AB sequences showed 86% identity. The 3C-like cleavage sites on the coronaviral polyproteins are highly conserved. Based on the near-identical substrate specificities and high sequence identities, we are of the opinion that some of the previous progress of specific inhibitors development for the SARS-CoV enzyme can be conferred on its SARS-CoV-2 counterpart. With the 3CL<ns4:sup>pro</ns4:sup> molecular model, we performed virtual screening for purchasable drugs and proposed 16 candidates for consideration. Among these, the antivirals ledipasvir or velpatasvir are particularly attractive as therapeutics to combat the new coronavirus with minimal side effects, commonly fatigue and headache. The drugs Epclusa (velpatasvir/sofosbuvir) and Harvoni (ledipasvir/sofosbuvir) could be very effective owing to their dual inhibitory actions on two viral enzymes.</ns4:p>

SARS-CoV-2, the causative agent of COVID-19, has caused more than 60 million cases worldwide with almost 1.5 million deaths as of November 2020. Repurposing existing drugs is the most rapid path to clinical intervention for emerging diseases.

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.

According to the World Health Organization (WHO), in the second half of 2022, there are about 606 million confirmed cases of COVID-19 and almost 6,500,000 deaths around the world. A pandemic was declared by the WHO in March 2020 when the new coronavirus spread around the world. The short time between the first cases in Wuhan and the declaration of a pandemic initiated the search for ways to stop the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or to attempt to cure the disease COVID-19. More than ever, research groups are developing vaccines, drugs, and immunobiological compounds, and they are even trying to repurpose drugs in an increasing number of clinical trials. There are great expectations regarding the vaccine’s effectiveness for the prevention of COVID-19. However, producing sufficient doses of vaccines for the entire population and SARS-CoV-2 variants are challenges for pharmaceutical industries. On the contrary, efforts have been made to create different vaccines with different approaches so that they can be used by the entire population. Here, we summarize about 8162 clinical trials, showing a greater number of drug clinical trials in Europe and the United States and less clinical trials in low-income countries. Promising results about the use of new drugs and drug repositioning, monoclonal antibodies, convalescent plasma, and mesenchymal stem cells to control viral infection/replication or the hyper-inflammatory response to the new coronavirus bring hope to treat the disease.

This work is a bibliographic review. The search for the necessary information was carried out in the months of November 2022 and January 2023. The databases used were as follows: Pubmed, Academic Google, Scielo, Scopus, and Cochrane library. Results: In total, 101 articles were selected after a review of 486 articles from databases and after applying the inclusion and exclusion criteria. The update on the molecular mechanism of human coronavirus (HCoV) infection was reviewed, describing possible therapeutic targets in the viral response phase. There are different strategies to prevent or hinder the introduction of the viral particle, as well as the replicative mechanism ((protease inhibitors and RNA-dependent RNA polymerase (RdRp)). The second phase of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) involves the activation of hyperinflammatory cascades of the host’s immune system. It is concluded that there are potential therapeutic targets and drugs under study in different proinflammatory pathways such as hydroxychloroquine, JAK inhibitors, interleukin 1 and 6 inhibitors, and interferons.

Context: The whole universe is facing a coronavirus catastrophe, and prompt treatment for the health crisis is primarily significant. The primary way to improve health conditions in this battle is to boost our immunity and alter our diet patterns. A common bulb veggie used to flavor cuisine is garlic. Compounds in the plant that are physiologically active are present, contributing to its pharmacological characteristics. Among several food items with nutritional value and immunity improvement, garlic stood predominant and more resourceful natural antibiotic with a broad spectrum of antiviral potency against diverse viruses. However, earlier reports have depicted its efficacy in the treatment of a variety of viral illnesses. Nonetheless, there is no information on its antiviral activities and underlying molecular mechanisms. Objectives: The bioactive compounds in garlic include organosulfur (allicin and alliin) and flavonoid (quercetin) compounds. These compounds have shown immunomodulatory effects and inhibited attachment of coronavirus to the angiotensin-converting enzyme 2 (ACE2) receptor and the Mpro of SARS-CoV-2. Further, we have discussed the contradictory impacts of garlic used as a preventive measure against the novel coronavirus. Method: The GC/MS analysis revealed 18 active chemicals, including 17 organosulfur compounds in garlic. Using the molecular docking technique, we report for the first time the inhibitory effect of the under-consideration compounds on the host receptor ACE2 protein in the human body, providing a crucial foundation for understanding individual compound coronavirus resistance on the main protease protein of SARS-CoV-2. Allyl disulfide and allyl trisulfide, which make up the majority of the compounds in garlic, exhibit the most potent activity. Results: Conventional medicine has proven its efficiency from ancient times. Currently, our article's prime spotlight was on the activity of Allium sativum on the relegation of viral load and further highlighted artificial intelligence technology to study the attachment of the allicin compound to the SARS-CoV-2 receptor to reveal its efficacy. Conclusions: The COVID-19 pandemic has triggered interest among researchers to conduct future research on molecular docking with clinical trials before releasing salutary remedies against the deadly malady.