Berbamine Hydrochloride

The pharmaceutical industry and academia are continuously searching for novel and effective anticancer lead compounds to ensure patient safety, provide a cure, and surpass all other obstacles. Given the indeterminate nature of cancer etiology, the importance of drugs capable of targeting multiple pathways cannot be overstated. Among naturally occurring compounds, bisbenzylisoquinoline (BBIQ) alkaloids, such as berberine, tetrandrine, chelidonine, and berbamine, have demonstrated significant anticancer potential by modulating diverse signaling pathways. Several of these compounds are currently in clinical trials, highlighting their relevance in cancer treatment. This review emphasizes the need for further investigation into the anticancer properties of BBIQ alkaloids, particularly those isolated from eight Cyclea species in India. With around 27 BBIQ alkaloids identified, these compounds hold promise, especially in combating multidrug resistance—a critical challenge in cancer therapy. Given the rising cancer incidence, these alkaloids warrant a deeper exploration of their therapeutic potential.

SARS-CoV-2, the causative virus of COVID-19, continues to threaten global public health. COVID-19 is a multi-organ disease, causing not only respiratory distress, but also extrapulmonary manifestations, including gastrointestinal symptoms with SARS-CoV-2 RNA shedding in stool long after respiratory clearance. Despite global vaccination and existing antiviral treatments, variants of concern are still emerging and circulating. Of note, new Omicron BA.5 sublineages both increasingly evade neutralizing antibodies and demonstrate an increased preference for entry via the endocytic entry route. Alternative to direct-acting antivirals, host-directed therapies interfere with host mechanisms hijacked by viruses, and enhance cell-mediated resistance with a reduced likelihood of drug resistance development. Here, we demonstrate that the autophagy-blocking therapeutic berbamine dihydrochloride robustly prevents SARS-CoV-2 acquisition by human intestinal epithelial cells via an autophagy-mediated BNIP3 mechanism. Strikingly, berbamine dihydrochloride exhibited pan-antiviral activity against Omicron subvariants BA.2 and BA.5 at nanomolar potency, providing a proof of concept for the potential for targeting autophagy machinery to thwart infection of current circulating SARS-CoV-2 subvariants. Furthermore, we show that autophagy-blocking therapies limited virus-induced damage to intestinal barrier function, affirming the therapeutic relevance of autophagy manipulation to avert the intestinal permeability associated with acute COVID-19 and post-COVID-19 syndrome. Our findings underscore that SARS-CoV-2 exploits host autophagy machinery for intestinal dissemination and indicate that repurposed autophagy-based antivirals represent a pertinent therapeutic option to boost protection and ameliorate disease pathogenesis against current and future SARS-CoV-2 variants of concern.