Dual action anti‐inflammatory/antiviral isoquinoline alkaloids as potent naturally occurring anti‐SARS‐CoV‐2 agents: A combined pharmacological and medicinal chemistry perspective

Abstract

In the search for compounds that inhibit the SARS‐CoV‐2 after the onset of the COVID‐19 pandemic, isoquinoline‐containing alkaloids have been identified as compounds with high potential to fight the disease. In addition to having strong antiviral activities, most of these alkaloids have significant anti‐inflammatory effects which are often manifested through the inhibition of a promising host‐based anti‐COVID‐19 target, the p38 MAPK signaling pathway. In the present review, our pharmacological and medicinal chemistry evaluation resulted in highlighting the potential of anti‐SARS‐CoV‐2 isoquinoline‐based alkaloids for the treatment of COVID‐19 patients. Considering critical parameters of the antiviral and anti‐inflammatory activities, mechanism of action, as well as toxicity/safety profile, we introduce the alkaloids emetine, cephaeline, and papaverine as high‐potential therapeutic agents for use in the treatment of COVID‐19. Although preclinical studies confirm that some isoquinoline‐based alkaloids reviewed in this study have a high potential to inhibit the SARS‐CoV‐2, their entry into drug regimens of COVID‐19 patients requires further clinical trial studies and toxicity evaluation.

Long COVID‐19 gastrointestinal related disorders and traditional Chinese medicine: A network target‐based approach

“…A recent report by Valipour, Hosseini, et al (2023) analyzed many isoquinoline alkaloids as potential SARS-CoV-2 inhibitors. From this study, papaverine (Figure 11) (from Papaver somniferum L.) emerges as very promising for COVID-19 treatment.…”

“…Isoquinoline alkaloids, widely used in TCM, possess anti‐SARS‐CoV‐2 and anti‐inflammatory effects (Valipour, Hosseini, et al, 2023), making them of great potential to alleviate gastrointestinal disorders related to COVID‐19.…”

Recent Applications of Protoberberines as Privileged Starting Materials for the Development of Novel Broad-Spectrum Antiviral Agents: A Concise Review (2017–2023)

“…Isoquinoline alkaloids make up a well-known class of natural bioactive compounds, which are mostly considered for their impressive antiviral and anti-inflammatory activities. In our recent studies, we have focused on the description of antiviral activities and therapeutic capabilities of different derivatives of these alkaloids against severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infectivity. , Berberine is the most famous member of this category, which is mostly considered for their impressive antiviral activities. Since a review study has recently been published regarding the antiviral activity of berberine, we only mention here the results of some studies published on the broad-spectrum antiviral activity of berberine in the past decade.…”

“…From a structural point of view, berberine is a cationic quaternary ammonium salt made by two fused scaffolds, isoquinoline and 3,4-dihydroisoquinoline. In terms of flexibility, the berberine has a rigid backbone consisting of four interconnected hexagonal rings A to D (Figure A) …”

Antimicrobial Properties of Capsaicin: Available Data and Future Research Perspectives

“…In the last decades there has been an increasing interest in the development of new antimicrobial substances from plants, as evidenced by a multitude of research on the subject (e.g., [3][4][5][6][7][8][9][10][11][12][13][14][15][16]). This renewed interest is based on the long-standing medical practices of various traditional medical systems, where plants and their derived extracts have been reported to have a host of applications.…”