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Salvianolic acid A for COVID-19

Salvianolic acid A has been reported as potentially beneficial for treatment of COVID-19. We have not reviewed these studies. See all other treatments.
Szabó et al., Natural products as a source of Coronavirus entry inhibitors, Frontiers in Cellular and Infection Microbiology, doi:10.3389/fcimb.2024.1353971
The COVID-19 pandemic has had a significant and lasting impact on the world. Four years on, despite the existence of effective vaccines, the continuous emergence of new SARS-CoV-2 variants remains a challenge for long-term immunity. Additionally, there remain few purpose-built antivirals to protect individuals at risk of severe disease in the event of future coronavirus outbreaks. A promising mechanism of action for novel coronavirus antivirals is the inhibition of viral entry. To facilitate entry, the coronavirus spike glycoprotein interacts with angiotensin converting enzyme 2 (ACE2) on respiratory epithelial cells. Blocking this interaction and consequently viral replication may be an effective strategy for treating infection, however further research is needed to better characterize candidate molecules with antiviral activity before progressing to animal studies and clinical trials. In general, antiviral drugs are developed from purely synthetic compounds or synthetic derivatives of natural products such as plant secondary metabolites. While the former is often favored due to the higher specificity afforded by rational drug design, natural products offer several unique advantages that make them worthy of further study including diverse bioactivity and the ability to work synergistically with other drugs. Accordingly, there has recently been a renewed interest in natural product-derived antivirals in the wake of the COVID-19 pandemic. This review provides a summary of recent research into coronavirus entry inhibitors, with a focus on natural compounds derived from plants, honey, and marine sponges.
Wang et al., Stand Up to Stand Out: Natural Dietary Polyphenols Curcumin, Resveratrol, and Gossypol as Potential Therapeutic Candidates against Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Nutrients, doi:10.3390/nu15183885
The COVID-19 pandemic has stimulated collaborative drug discovery efforts in academia and the industry with the aim of developing therapies and vaccines that target SARS-CoV-2. Several novel therapies have been approved and deployed in the last three years. However, their clinical application has revealed limitations due to the rapid emergence of viral variants. Therefore, the development of next-generation SARS-CoV-2 therapeutic agents with a high potency and safety profile remains a high priority for global health. Increasing awareness of the “back to nature” approach for improving human health has prompted renewed interest in natural products, especially dietary polyphenols, as an additional therapeutic strategy to treat SARS-CoV-2 patients, owing to its good safety profile, exceptional nutritional value, health-promoting benefits (including potential antiviral properties), affordability, and availability. Herein, we describe the biological properties and pleiotropic molecular mechanisms of dietary polyphenols curcumin, resveratrol, and gossypol as inhibitors against SARS-CoV-2 and its variants as observed in in vitro and in vivo studies. Based on the advantages and disadvantages of dietary polyphenols and to obtain maximal benefits, several strategies such as nanotechnology (e.g., curcumin-incorporated nanofibrous membranes with antibacterial-antiviral ability), lead optimization (e.g., a methylated analog of curcumin), combination therapies (e.g., a specific combination of plant extracts and micronutrients), and broad-spectrum activities (e.g., gossypol broadly inhibits coronaviruses) have also been emphasized as positive factors in the facilitation of anti-SARS-CoV-2 drug development to support effective long-term pandemic management and control.
Onyango, O., In Silico Models for Anti-COVID-19 Drug Discovery: A Systematic Review, Advances in Pharmacological and Pharmaceutical Sciences, doi:10.1155/2023/4562974
The coronavirus disease 2019 (COVID-19) is a severe worldwide pandemic. Due to the emergence of various SARS-CoV-2 variants and the presence of only one Food and Drug Administration (FDA) approved anti-COVID-19 drug (remdesivir), the disease remains a mindboggling global public health problem. Developing anti-COVID-19 drug candidates that are effective against SARS-CoV-2 and its various variants is a pressing need that should be satisfied. This systematic review assesses the existing literature that used in silico models during the discovery procedure of anti-COVID-19 drugs. Cochrane Library, Science Direct, Google Scholar, and PubMed were used to conduct a literature search to find the relevant articles utilizing the search terms “In silico model,” “COVID-19,” “Anti-COVID-19 drug,” “Drug discovery,” “Computational drug designing,” and “Computer-aided drug design.” Studies published in English between 2019 and December 2022 were included in the systematic review. From the 1120 articles retrieved from the databases and reference lists, only 33 were included in the review after the removal of duplicates, screening, and eligibility assessment. Most of the articles are studies that use SARS-CoV-2 proteins as drug targets. Both ligand-based and structure-based methods were utilized to obtain lead anti-COVID-19 drug candidates. Sixteen articles also assessed absorption, distribution, metabolism, excretion, toxicity (ADMET), and drug-likeness properties. Confirmation of the inhibitory ability of the candidate leads by in vivo or in vitro assays was reported in only five articles. Virtual screening, molecular docking (MD), and molecular dynamics simulation (MDS) emerged as the most commonly utilized in silico models for anti-COVID-19 drug discovery.
Krüger et al., Discovery of Polyphenolic Natural Products as SARS-CoV-2 Mpro Inhibitors for COVID-19, Pharmaceuticals, doi:10.3390/ph16020190
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has forced the development of direct-acting antiviral drugs due to the coronavirus disease 2019 (COVID-19) pandemic. The main protease of SARS-CoV-2 is a crucial enzyme that breaks down polyproteins synthesized from the viral RNA, making it a validated target for the development of SARS-CoV-2 therapeutics. New chemical phenotypes are frequently discovered in natural goods. In the current study, we used a fluorogenic assay to test a variety of natural products for their ability to inhibit SARS-CoV-2 Mpro. Several compounds were discovered to inhibit Mpro at low micromolar concentrations. It was possible to crystallize robinetin together with SARS-CoV-2 Mpro, and the X-ray structure revealed covalent interaction with the protease’s catalytic Cys145 site. Selected potent molecules also exhibited antiviral properties without cytotoxicity. Some of these powerful inhibitors might be utilized as lead compounds for future COVID-19 research.
Tsuji, M., Virtual Screening and Quantum Chemistry Analysis for SARS-CoV-2 RNA-Dependent RNA Polymerase Using the ChEMBL Database: Reproduction of the Remdesivir-RTP and Favipiravir-RTP Binding Modes Obtained from Cryo-EM Experiments with High Binding Affinity, International Journal of Molecular Sciences, doi:10.3390/ijms231911009
The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as the pathogenic cause of coronavirus disease 2019 (COVID-19). The RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is a potential target for the treatment of COVID-19. An RdRp complex:dsRNA structure suitable for docking simulations was prepared using a cryo-electron microscopy (cryo-EM) structure (PDB ID: 7AAP; resolution, 2.60 Å) that was reported recently. Structural refinement was performed using energy calculations. Structure-based virtual screening was performed using the ChEMBL database. Through 1,838,257 screenings, 249 drugs (37 approved, 93 clinical, and 119 preclinical drugs) were predicted to exhibit a high binding affinity for the RdRp complex:dsRNA. Nine nucleoside triphosphate analogs with anti-viral activity were included among these hit drugs, and among them, remdesivir-ribonucleoside triphosphate and favipiravir-ribonucleoside triphosphate adopted a similar docking mode as that observed in the cryo-EM structure. Additional docking simulations for the predicted compounds with high binding affinity for the RdRp complex:dsRNA suggested that 184 bioactive compounds could be anti-SARS-CoV-2 drug candidates. The hit bioactive compounds mainly consisted of a typical noncovalent major groove binder for dsRNA. Three-layer ONIOM (MP2/6-31G:AM1:AMBER) geometry optimization calculations and frequency analyses (MP2/6-31G:AMBER) were performed to estimate the binding free energy of a representative bioactive compound obtained from the docking simulation, and the fragment molecular orbital calculation at the MP2/6-31G level of theory was subsequently performed for analyzing the detailed interactions. The procedure used in this study represents a possible strategy for discovering anti-SARS-CoV-2 drugs from drug libraries that could significantly shorten the clinical development period for drug repositioning.
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. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment 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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