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Venetoclax for COVID-19

Venetoclax has been reported as potentially beneficial for treatment of COVID-19. We have not reviewed these studies. See all other treatments.
Chen et al., Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CLpro) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates, F1000Research, doi:10.12688/f1000research.22457.2
<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>
Day et al., Multidisciplinary Approaches Identify Compounds that Bind to Human ACE2 or SARS-CoV-2 Spike Protein as Candidates to Block SARS-CoV-2–ACE2 Receptor Interactions, mBio, doi:10.1128/mBio.03681-20
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.
Chen et al., A high-throughput screen for TMPRSS2 expression identifies FDA-approved compounds that can limit SARS-CoV-2 entry, Nature Communications, doi:10.1038/s41467-021-24156-y
AbstractSARS-CoV-2 (2019-nCoV) is the pathogenic coronavirus responsible for the global pandemic of COVID-19 disease. The Spike (S) protein of SARS-CoV-2 attaches to host lung epithelial cells through the cell surface receptor ACE2, a process dependent on host proteases including TMPRSS2. Here, we identify small molecules that reduce surface expression of TMPRSS2 using a library of 2,560 FDA-approved or current clinical trial compounds. We identify homoharringtonine and halofuginone as the most attractive agents, reducing endogenous TMPRSS2 expression at sub-micromolar concentrations. These effects appear to be mediated by a drug-induced alteration in TMPRSS2 protein stability. We further demonstrate that halofuginone modulates TMPRSS2 levels through proteasomal-mediated degradation that involves the E3 ubiquitin ligase component DDB1- and CUL4-associated factor 1 (DCAF1). Finally, cells exposed to homoharringtonine and halofuginone, at concentrations of drug known to be achievable in human plasma, demonstrate marked resistance to SARS-CoV-2 infection in both live and pseudoviral in vitro models. Given the safety and pharmacokinetic data already available for the compounds identified in our screen, these results should help expedite the rational design of human clinical trials designed to combat active COVID-19 infection.
Moura et al., 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.
Atoum et al., Paving New Roads Using Allium sativum as a Repurposed Drug and Analyzing its Antiviral Action Using Artificial Intelligence Technology, Iranian Journal of Pharmaceutical Research, doi:10.5812/ijpr-131577
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.
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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