Challenges Based on Antiplasmodial and Antiviral Activities of 7-Chloro-4-aminoquinoline Derivatives.

We report the structural functionalization of the terminal amino group of N1 -(7-chloroquinolin-4-yl) butane-1,4-diamine, leading to a series of 7-chloro-4-aminoquinoline derivatives, and their evaluation as potent anti-malarial and anti-viral agents. Some compounds exhibited promising anti-malarial effects against the Plasmodium falciparum 3D7 (chloroquine-sensitive) and Dd2 (chloroquine-resistant) strains. In addition, these compounds were assayed in vitro against influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Compound 5 h, bearing an N-mesityl thiourea group, displayed pronounced anti-infectious effects against malaria, IAV, and SARS-CoV-2. These results provide new insights into drug discovery for the prevention or treatment of malaria and virus co-infection.

Anti-influenza Virus Activity of Methylthio-Formycin Distinct From That of T-705.

Seasonal influenza virus epidemics result in severe illness, and occasionally influenza pandemics cause significant morbidity and mortality, although vaccines and anti-influenza virus drugs are available. By screening an in-house library, we identified methylthio-formycin (SMeFM), an adenosine analog, as a potent inhibitor of influenza virus propagation. SMeFM inhibited the propagation of influenza A and B viruses (IC50: 34.1 and 37.9 nM, respectively) and viruses showing reduced susceptibility to baloxavir and neuraminidase inhibitors but not T-705 (Favipiravir). However, the combination of T-705 and SMeFM inhibited the propagation of the influenza virus not in an antagonistic but in a slightly synergistic manner, suggesting that SMeFM has targets distinct from that of T-705. SMeFM induced A-to-C transversion mutations in virus genome RNA, and SMeFM triphosphate did not inhibit in vitro viral RNA synthesis. Our results show that SMeFM inhibits the propagation of the influenza virus by a mechanism different from that of T-705 and is a potential drug candidate to develop for anti-influenza drug.

Isolation and identification of two new compounds from the seeds of Moringa oleifera and their antiviral and anti-inflammatory activities.

Eleven compounds were isolated from methanol extract taken from Moringa oleifera seeds, including two previously unknown and nine known compounds. These compounds were authenticated as a carbamate, three phenylglycosides, four phenol glycosides, two nucleosides, and one flavonoid. Their chemical structures were elucidated using 1 D/2D nuclear magnetic resonance and high resolution-MS. Antivirus activity analyses revealed that Moringa A, glucomoringin, and Vitexin possessed strong inhibitory effects against the H1N1 virus, having IC50 values in the range of IC50 = 0.26 ± 0.03, 0.98 ± 0.17, and 3.42 ± 0.37 µg/mL, respectively. Furthermore, these three compounds could decrease the levels of TNF-α, IL-6, and IL-1ß, which occur in hosts because of H1N1 infections.