Cepharanthine for COVID-19

To effectively respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an increasing number of researchers are focusing on the antiviral activity of cepharanthine (CEP), which is a clinically approved drug being used for over 70 years. This review aims to provide a brief overview of CEP and summarize its recent findings in quantitative analysis, pharmacokinetics, therapeutic potential, and mechanism in antiviral and anti-SARS-CoV-2 activity. Given its remarkable capacity against SARS-CoV-2 infection in vitro and in vivo, with its primary target organ being the lungs, and its good pharmacokinetic profile; mature and stable manufacturing technique; and its advantages of safety, effectiveness, and accessibility, CEP has become a promising drug candidate for treating COVID-19 despite being an old drug.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped respiratory β coronavirus that causes coronavirus disease (COVID-19), leading to a deadly pandemic that has claimed millions of lives worldwide. Like other coronaviruses, the SARS-CoV-2 genome also codes for non-structural proteins (NSPs). These NSPs are found within open reading frame 1a (ORF1a) and open reading frame 1ab (ORF1ab) of the SARS-CoV-2 genome and encode NSP1 to NSP11 and NSP12 to NSP16, respectively. This study aimed to collect the available literature regarding NSP inhibitors. In addition, we searched the natural product database looking for similar structures. The results showed that similar structures could be tested as potential inhibitors of the NSPs.

AbstractThe search for an effective drug is still urgent for COVID-19 as no drug with proven clinical efficacy is available. Finding the new purpose of an approved or investigational drug, known as drug repurposing, has become increasingly popular in recent years. We propose here a new drug repurposing approach for COVID-19, based on knowledge graph (KG) embeddings. Our approach learns “ensemble embeddings” of entities and relations in a COVID-19 centric KG, in order to get a better latent representation of the graph elements. Ensemble KG-embeddings are subsequently used in a deep neural network trained for discovering potential drugs for COVID-19. Compared to related works, we retrieve more in-trial drugs among our top-ranked predictions, thus giving greater confidence in our prediction for out-of-trial drugs. For the first time to our knowledge, molecular docking is then used to evaluate the predictions obtained from drug repurposing using KG embedding. We show that Fosinopril is a potential ligand for the SARS-CoV-2 nsp13 target. We also provide explanations of our predictions thanks to rules extracted from the KG and instanciated by KG-derived explanatory paths. Molecular evaluation and explanatory paths bring reliability to our results and constitute new complementary and reusable methods for assessing KG-based drug repurposing.

Over the past few years, COVID-19 has caused widespread suffering worldwide. There is great research potential in this domain and it is also necessary. The main objective of this study was to identify potential inhibitors against acid sphingomyelinase (ASM) in order to prevent coronavirus infection. Experimental studies revealed that SARS-CoV-2 causes activation of the acid sphingomyelinase/ceramide pathway, which in turn facilitates the viral entry into the cells. The objective was to inhibit acid sphingomyelinase activity in order to prevent the cells from SARS-CoV-2 infection. Previous studies have reported functional inhibitors against ASM (FIASMAs). These inhibitors can be exploited to block the entry of SARS-CoV-2 into the cells. To achieve our objective, a drug library containing 257 functional inhibitors of ASM was constructed. Computational molecular docking was applied to dock the library against the target protein (PDB: 5I81). The potential binding site of the target protein was identified through structural alignment with the known binding pocket of a protein with a similar function. AutoDock Vina was used to carry out the docking steps. The docking results were analyzed and the inhibitors were screened based on their binding affinity scores and ADME properties. Among the 257 functional inhibitors, Dutasteride, Cepharanthine, and Zafirlukast presented the lowest binding affinity scores of −9.7, −9.6, and −9.5 kcal/mol, respectively. Furthermore, computational ADME analysis of these results revealed Cepharanthine and Zafirlukast to have non-toxic properties. To further validate these findings, the top two inhibitors in complex with the target protein were subjected to molecular dynamic simulations at 100 ns. The molecular interactions and stability of these compounds revealed that these inhibitors could be a promising tool for inhibiting SARS-CoV-2 infection.

The highly contagious coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic and public health emergency as it has taken the lives of over 5.7 million in more than 180 different countries. This disease is characterized by respiratory tract symptoms, such as dry cough and shortness of breath, as well as other symptoms, including fever, chills, and fatigue. COVID-19 is also characterized by the excessive release of cytokines causing inflammatory injury to the lungs and other organs. It is advised to undergo precautionary measures, such as vaccination, social distancing, use of masks, hygiene, and a healthy diet. This review is aimed at summarizing the pathophysiology of COVID-19 and potential biologically active compounds (bioactive) found in plants and plant food. We conclude that many plant food bioactive compounds exhibit antiviral and anti-inflammatory properties and support in attenuating organ damage due to reduced cytokine release and improving the recovery process from COVID-19 infection.

The current pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) demands rapid identification of new antiviral molecules from the existing drugs. Drug repurposing is a significant alternative for pandemics and emerging diseases because of the availability of preclinical data, documented safety in clinic and possibility of immediate production and scalable capacity and supply. Several drugs such as ivermectin and hydroxy chloroquine have been repurposed as anti-SARS-CoV-2 agents, but the effect of these compounds in treating the COVID-19 patients remains sub-optimal. In the present study repurposed drug libraries consisting of 560 compounds from two different sources have been screened against SARS-CoV-2 isolate USA-WA1/2020 in Vero-E6 cell line and 24 compounds were found active. The SARS-CoV-2 virus propagated in Vero E6 cell line and used in screening the drug libraries was sequenced by Next Generation Sequencing to identify any mutations that may have accumulated in the virus genome. The whole genome sequencing data of SARS-CoV-2 showed 9 and 6 single nucleotide polymorphisms in spike protein with reference to Wuhan-Hu-1(NC045512.2) and USA/WA-CDC-WA1/2020 (MN985325.1) isolates respectively. The present study identified 24 compounds active against SARS-CoV-2 isolate USA-WA1/2020 out of 560 repurposed drugs from two libraries. The IC-50 values of the identified hits range from 0.4 µM to 16 µM. Further studies on the repurposed drugs identified in the present screen may be helpful in the rapid development of antiviral drugs against SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) induced by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has impacted the lives and wellbeing of many people. This globally widespread disease poses a significant public health concern that urges to discover an effective treatment. This review paper discusses the effectiveness of repurposed drugs used to treat COVID-19 and potential novel therapies for COVID-19. Among the various repurposed drugs, remdesivir is the only agent approved by the Food and Drug Administration (FDA) to treat COVID-19. On the other hand, several drugs have been listed in the Emergency Use Authorization (EUA) by the FDA to treat COVID-19, including casirivimab and imdevimab, baricitinib (in combination with remdesivir), bamlanivimab, tocilizumab, and IL-6 inhibitors. In addition, in vitro and clinical studies have suggested cepharanthine, sotrovimab, and XAV-19 as potential treatments to manage COVID-19. Due to inadequate understanding of COVID-19 and the rapid mutation of SARS-CoV-2, COVID-19 remains a threat to global public health, with vaccination considered the most effective method to decrease COVID-19 transmission currently. Nevertheless, with the intense efforts of clinical researchers globally, more promising treatments for COVID-19 will be established in the future.