Ugonin J Acts as a SARS-CoV-2 3C-like Protease Inhibitor and Exhibits Anti-inflammatory Properties

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes severe “flu-like” symptoms that can progress to acute respiratory distress syndrome (ARDS), pneumonia, renal failure, and death. From the therapeutic perspective, 3-chymotrypsin-like protein (3CLpro) is a plausible target for direct-acting antiviral agents because of its indispensable role in viral replication. The flavonoid ugonin J (UJ) has been reported to have antioxidative and anti-inflammatory activities. However, the potential of UJ as an antiviral agent remains unexplored. In this study, we investigated the therapeutic activity of UJ against SARS-CoV-2 infection. Importantly, UJ has a distinct inhibitory activity against SARS-CoV-2 3CLpro, compared to luteolin, kaempferol, and isokaempferide. Specifically, UJ blocks the active site of SARS-CoV-2 3CLpro by forming hydrogen bonding and van der Waals interactions with H163, M165 and E166, G143 and C145, Q189, and P168 in subsites S1, S1′, S2, and S4, respectively. In addition, UJ forms strong, stable interactions with core pharmacophore anchors of SARS-CoV-2 3CLpro in a computational model. UJ shows consistent anti-inflammatory activity in inflamed human alveolar basal epithelial A549 cells. Furthermore, UJ has a 50% cytotoxic concentration (CC50) and a 50% effective concentration (EC50) values of about 783 and 2.38 µM, respectively, with a selectivity index (SI) value of 329, in SARS-CoV-2-infected Vero E6 cells. Taken together, UJ is a direct-acting antiviral that obstructs the activity of a fundamental protease of SARS-CoV-2, offering the therapeutic potential for SARS-CoV-2 infection.

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Statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor)-based therapy for hepatitis C virus (HCV) infection-related diseases in the era of direct-acting antiviral agents

F1000Research ◽

10.12688/f1000research.7970.2 ◽

2016 ◽

Vol 5 ◽

pp. 223 ◽

Cited By ~ 1

Author(s):

Sara Sobhy Kishta ◽

Reem El-Shenawy ◽

Sobhy Ahmed Kishta

Keyword(s):

Clinical Trials ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Antiviral Agents ◽

Antiviral Agent ◽

Viral Clearance ◽

Hcv Infection ◽

Direct Acting Antiviral ◽

Direct Acting ◽

Direct Acting Antiviral Agents

Recent improvements have been made in the treatment of hepatitis C virus (HCV) infection with the introduction of direct-acting antiviral agents (DAAs). However, despite successful viral clearance, many patients continue to have HCV-related disease progression. Therefore, new treatments must be developed to achieve viral clearance and prevent the risk of HCV-related diseases. In particular, the use of pitavastatin together with DAAs may improve the antiviral efficacy as well as decrease the progression of liver fibrosis and the incidence of HCV-related hepatocellular carcinoma. To investigate the management methods for HCV-related diseases using pitavastatin and DAAs, clinical trials should be undertaken. However, concerns have been raised about potential drug interactions between statins and DAAs. Therefore, pre-clinical trials using a replicon system, human hepatocyte-like cells, human neurons and human cardiomyocytes from human-induced pluripotent stem cells should be conducted. Based on these pre-clinical trials, an optimal direct-acting antiviral agent could be selected for combination with pitavastatin and DAAs. Following the pre-clinical trial, the combination of pitavastatin and the optimal direct-acting antiviral agent should be compared to other combinations of DAAs (e.g., sofosbuvir and velpatasvir) according to the antiviral effect on HCV infection, HCV-related diseases and cost-effectiveness.

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Statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor)-based therapy for hepatitis C virus (HCV) infection-related diseases in the era of direct-acting antiviral agents

F1000Research ◽

10.12688/f1000research.7970.3 ◽

2017 ◽

Vol 5 ◽

pp. 223

Author(s):

Sara Sobhy Kishta ◽

Sobhy Ahmed Kishta ◽

Reem El-Shenawy

Keyword(s):

Clinical Trials ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Antiviral Agents ◽

Antiviral Agent ◽

Viral Clearance ◽

Hcv Infection ◽

Direct Acting Antiviral ◽

Direct Acting ◽

Direct Acting Antiviral Agents

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Viekira Pak Induced Fatal Lactic Acidosis: A Case Report of an Unusual Side Effect

Case Reports in Hepatology ◽

10.1155/2016/8627139 ◽

2016 ◽

Vol 2016 ◽

pp. 1-3 ◽

Cited By ~ 2

Author(s):

Molham Abdulsamad ◽

Ariyo Ihimoyan

Keyword(s):

Lactic Acidosis ◽

Side Effect ◽

Antiviral Agents ◽

Antiviral Agent ◽

Direct Acting Antiviral ◽

First Case ◽

Safety Warning ◽

Chronic Hcv ◽

Direct Acting ◽

Direct Acting Antiviral Agents

Viekira Pak is a new direct-acting antiviral agent that has an excellent efficacy in treating patients with chronic HCV. FDA released a safety warning that Viekira Pak can cause serious liver injury mostly in patients with underlying advanced liver disease. We report the first case of fatal lactic acidosis presenting 3 days after initiating therapy with Viekira Pak. Although it is very hard to precisely determine the cause of lactic acidosis, our case highlights an unusual side effect that ensued after starting the medication. Given the complexity of drug-drug interactions that can happen with the new direct-acting antiviral agents and the paucity of data regarding coadministration and methods of monitoring, a thorough review should be pursued prior to initiating these medications.

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Statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor)-based therapy for hepatitis C virus (HCV) infection-related diseases in the era of direct-acting antiviral agents

F1000Research ◽

10.12688/f1000research.7970.1 ◽

2016 ◽

Vol 5 ◽

pp. 223 ◽

Cited By ~ 1

Author(s):

Sara Sobhy Kishta ◽

Reem El-Shenawy ◽

Sobhy Ahmed Kishta

Keyword(s):

Clinical Trials ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Antiviral Agents ◽

Antiviral Agent ◽

Viral Clearance ◽

Hcv Infection ◽

Direct Acting Antiviral ◽

Direct Acting ◽

Direct Acting Antiviral Agents

Recent improvements have been made in the treatment of hepatitis C virus (HCV) infection with the introduction of direct-acting antiviral agents (DAAs). However, despite successful viral clearance, many patients continue to have HCV-related disease progression. Therefore, new treatments must be developed to achieve viral clearance and prevent the risk of HCV-related diseases. In particular, the use of pitavastatin together with DAAs may improve the antiviral efficacy as well as decrease the progression of liver fibrosis and the incidence of HCV-related hepatocellular carcinoma. To investigate the management methods for HCV-related diseases using pitavastatin and DAAs, clinical trials should be undertaken. However, concerns have been raised about potential drug interactions between statins and DAAs. Therefore, pre-clinical trials using a replicon system and human hepatocyte-like cells from human-induced pluripotent stem cells should be conducted. Based on these pre-clinical trials, an optimal direct-acting antiviral agent could be selected for combination with pitavastatin and DAAs. Following the pre-clinical trial, the combination of pitavastatin and the optimal direct-acting antiviral agent should be compared to other combinations of DAAs (e.g., sofosbuvir and velpatasvir) according to the antiviral effect on HCV infection, HCV-related diseases and cost-effectiveness.

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