Since the efficiency in the transcription of the HIV genome contributes to the success of viral replication and infectivity, we investigated the downregulating effects of the spirobisindole alkaloids globospiramine (1), deoxyvobtusine (2), and vobtusine lactone (3) from the endemic Philippine medicinal plant, Voacanga globosa, during HIV gene transcription. Alkaloids 1–3 were explored for their inhibitory activity on TNF-α-induced viral replication in two latently HIV-infected cell lines, OM10.1 and J-Lat. The induction of HIV replication from OM10.1 and J-Lat cells elicited by TNF-α was blocked by globospiramine (1) within noncytotoxic concentrations. Furthermore, globospiramine (1) was found to target the NF-ĸB activation cascade in a dose-dependent manner when the transcriptional step at which inhibitory activity is exerted was examined in TNF-α-induced 293 human cells using transient reporter (luciferase) gene expression systems (HIV LTR-luc, ĸB-luc, and mutant ĸB-luc). Interrogation through molecular docking against the NF-ĸB p50/p65 heterodimer and target sites of the subunits comprising the IKK complex revealed high binding affinities of globospiramine (1) against the S281 pocket of the p65 subunit (BE = −9.2 kcal/mol) and the IKKα activation loop (BE = −9.1 kcal/mol). These findings suggest globospiramine (1) as a molecular inspiration to discover new alkaloid-based anti-HIV derivatives.

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The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) emerged in December 2019 leading to a global pandemic and lockdowns in different countries including the Philippines. There is an oral antiviral treatment, Paxlovid, produced by Pfizer that is currently authorized for emergency use to treat COVID-19. However, there is still a necessity to discover specific antiviral drugs due to increasing cases worldwide. In this study, 56 cyanobacterial secondary metabolites were virtually screened for in silico inhibitory prospects against five main targeted proteins of SARS-CoV-2 involved in viral attachment, viral replication, and host immunity modulation mechanisms. Pharmacokinetic properties and toxicity predictions were also performed. Of the fifty-six secondary metabolites molecularly docked, compounds 1–7 showed favorable binding energy ranging from -10.9 to -8.0 kcal/mol against the spike’s ACE2 (angiotensin-converting enzyme 2) and GRP 78 (glucose-related protein 78) receptor binding domains, 3CLPRO (3-chymotrypsin-like protease), PLPRO (papain-like protease), and RdRp (RNA-dependent RNA-polymerase). Three compounds, scytonemin (1) a bisindole alkaloid dimer, cryptophycin (5) a macrolactam, and tjipanazole A2 (6) an indole alkaloid glucoside exhibited highest the binding affinities with BE’s ranging from -10.4 to -8.6 kcal/mol. Top-ranked ligands 1–7 also demonstrated favorable pharmacokinetics with low toxicity risks.