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Pelitinib for COVID-19

Pelitinib has been reported as potentially beneficial for treatment of COVID-19. We have not reviewed these studies. See all other treatments.
Günther et al., X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease, Science, doi:10.1126/science.abf7945
A large-scale screen to target SARS-CoV-2 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome is initially expressed as two large polyproteins. Its main protease, M pro , is essential to yield functional viral proteins, making it a key drug target. Günther et al. used x-ray crystallography to screen more than 5000 compounds that are either approved drugs or drugs in clinical trials. The screen identified 37 compounds that bind to M pro . High-resolution structures showed that most compounds bind at the active site but also revealed two allosteric sites where binding of a drug causes conformational changes that affect the active site. In cell-based assays, seven compounds had antiviral activity without toxicity. The most potent, calpeptin, binds covalently in the active site, whereas the second most potent, pelitinib, binds at an allosteric site. Science , this issue p. 642
Murer et al., Arrayed multicycle drug screens identify broadly acting chemical inhibitors for repurposing against SARS-CoV-2, bioRxiv, doi:10.1101/2021.03.30.437771
AbstractCoronaviruses (CoVs) circulate in humans and animals, and expand their host range by zoonotic and anthroponotic transmissions. Endemic human CoVs, such as 229E and OC43 cause limited respiratory disease, and elicit short term anti-viral immunity favoring recurrent infections. Yet, severe acute respir-atory syndrome (SARS)-CoV-2 spreads across the globe with unprecedented impact on societies and economics. The world lacks broadly effective and affordable anti-viral agents to fight the pandemic and reduce the death toll. Here, we developed an image-based multicycle replication assay for focus for-mation of α-coronavirus hCoV-229E-eGFP infected cells for screening with a chemical library of 5440 compounds arrayed in 384 well format. The library contained about 39% clinically used compounds, 26% in phase I, II or III clinical trials, and 34% in preclinical development. Hits were counter-selected against toxicity, and challenged with hCoV-OC43 and SARS-CoV-2 in tissue culture and human bronchial and nasal epithelial explant cultures from healthy donors. Fifty three compounds inhibited hCoV-229E-GFP, 39 of which at 50% effective concentrations (EC50) < 2μM, and were at least 2-fold separated from toxicity. Thirty nine of the 53 compounds inhibited the replication of hCoV-OC43, while SARS-CoV-2 was inhibited by 11 compounds in at least two of four tested cell lines. Six of the 11 compounds are FDA-approved, one of which is used in mouth wash formulations, and five are systemic and orally available. Here, we demonstrate that methylene blue (MB) and mycophenolic acid (MPA), two broadly available low cost compounds, strongly inhibited shedding of infectious SARS-CoV-2 at the apical side of the cultures, in either pre- or post-exposure regimens, with somewhat weaker effects on viral RNA release indicated by RT-qPCR measurements. Our study illustrates the power of full cycle screens in repurposing clinical compounds against SARS-CoV-2. Importantly, both MB and MPA reportedly act as immunosuppressants, making them interesting candidates to counteract the cytokine storms affecting COVID-19 patients.
Citarella et al., Recent Advances in SARS-CoV-2 Main Protease Inhibitors: From Nirmatrelvir to Future Perspectives, Biomolecules, doi:10.3390/biom13091339
The main protease (Mpro) plays a pivotal role in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is considered a highly conserved viral target. Disruption of the catalytic activity of Mpro produces a detrimental effect on the course of the infection, making this target one of the most attractive for the treatment of COVID-19. The current success of the SARS-CoV-2 Mpro inhibitor Nirmatrelvir, the first oral drug for the treatment of severe forms of COVID-19, has further focused the attention of researchers on this important viral target, making the search for new Mpro inhibitors a thriving and exciting field for the development of antiviral drugs active against SARS-CoV-2 and related coronaviruses.
Carabineiro et al., CuFe2O4 Magnetic Nanoparticles as Heterogeneous Catalysts for Synthesis of Dihydropyrimidinones as Inhibitors of SARS-CoV-2 Surface Proteins—Insights from Molecular Docking Studies, Processes, doi:10.3390/pr11082294
In this study, we present the highly efficient and rapid synthesis of substituted dihydropyrimidinone derivatives through an ultrasound-accelerated approach. We utilize copper ferrite (CuFe2O4) magnetic nanoparticles as heterogeneous catalysts, employing the well-known Biginelli reaction, under solvent-free conditions. The impact of the solvent, catalyst amount, and catalyst type on the reaction performance is thoroughly investigated. Our method offers several notable advantages, including facile catalyst separation, catalyst reusability for up to three cycles with the minimal loss of activity, a straightforward procedure, mild reaction conditions, and impressive yields, ranging from 79% to 95%, within short reaction times of 20 to 40 min. Furthermore, in the context of fighting COVID-19, we explore the potential of substituted dihydropyrimidinone derivatives as inhibitors of three crucial SARS-CoV-2 proteins. These proteins, glycoproteins, and proteases play pivotal roles in the entry, replication, and spread of the virus. Peptides and antiviral drugs targeting these proteins hold great promise in the development of effective treatments. Through theoretical molecular docking studies, we compare the binding properties of the synthesized dihydropyrimidinone derivatives with the widely used hydroxychloroquine molecule as a reference. Our findings reveal that some of the tested molecules exhibit superior binding characteristics compared to hydroxychloroquine, while others demonstrate comparable results. These results highlight the potential of our synthesized derivatives as effective inhibitors in the fight against SARS-CoV-2.
Please send us corrections, updates, or comments. c19early involves the extraction of over 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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