Tuberculosis (TB) remains a serious threat to global public health, responsible for an estimated 1.5 million mortalities in 2018. While there are available therapeutics for this infection, slow-acting drugs, poor patient compliance, drug toxicity, and drug resistance require the discovery of novel TB drugs. Discovering new and more potent antibiotics that target novel TB protein targets is an attractive strategy towards controlling the global TB epidemic. In silico strategies can be applied at multiple stages of the drug discovery paradigm to expedite the identification of novel anti-TB therapeutics. In this paper, we discuss the current TB treatment, emergence of drug resistance, and the effective application of computational tools to the different stages of TB drug discovery when combined with traditional biochemical methods. We will also highlight the strengths and points of improvement in in silico TB drug discovery research, as well as possible future perspectives in this field.

Natural products possess a wide range of biological and biochemical potentials, with plant-derived compounds being significant sources for discovering new drugs. In this study, extracts of Vitex negundo and Macaranga tanarius prepared with different solvents were tested for their antiviral activity against the original SARS-CoV-2 Wuhan strain and its variants using plaque assay, quantitative real time RT-PCR, and immunofluorescence assay (IFA). Our results showed that at their maximum non-toxic concentrations, Vitex-Dichloromethane (DCM) and Macaranga extracts significantly inhibited SARS-CoV-2 Wuhan strain growth in Vero E6 cells, showing a 5-log reduction in plaque assay and confirmed by IFA. Meanwhile, Vitex-Hexane showed moderate activity with a 2-log decrease. The inhibition was shown in a dose-dependent manner. The antiviral efficacy of these extracts was further demonstrated against various SARS-CoV-2 variants including Alpha, Beta, Delta, and Omicron. Both Vitex-DCM and Macaranga showed strong virucidal activity. In addition, Vitex-DCM and Macaranga inhibited the transcriptional activity of purified SARS-CoV-2 RdRp, indicating that RdRp inhibition may contribute to viral suppression as shown at the post-infection stage. Furthermore, combining Vitex-DCM or Macaranga with remdesivir showed a synergistic effect against SARS-CoV-2. These results suggest that Vitex negundo and Macaranga tanarius extracts are promising candidates for anti-SARS-CoV-2 treatments. Their synergy with remdesivir also underscores the potential of drug combinations in fighting SARS-CoV-2 and preventing the emergence of mutant variants.

Dengue is an infection transmitted by the Aedes mosquito and is considered a major public health concern in many tropical and Asian countries, including the Philippines. It is caused by the dengue virus (DENV) which belongs to the Flaviviridae family and has four serotypes. The non-structural protein 5 (NS5), which consists of an MTase domain and an RdRp domain, is the largest and most conserved protein among flaviviruses and thus a potential target against DENV. However, there are very limited studies on the functional homodimer structure of NS5. Through molecular dynamics, it was found that residues 458–470, 583–586, 630–637, 743–744, and 890–900 of monomer A and residues 14–24, 311–315, and 462–464 of monomer B undergo essential motions for the conformational changes in the RdRp template tunnel and GTP binding in the MTase domain. Through the analysis of these motions, it was also proposed that in the dimeric structure of NS5 only one pair of domains contribute to the function of the protein. Other essential residues, specifically A-ASP533, A-LYS689, A-ARG620, A-ARG688, A-SER710, B-ARG620, B-LYS689, A-GLU40, A-ARG262, A-GLU267, A-ARG673, and B-ARG673, were also identified to play important roles in the information flow necessary for the function of the protein. In particular, shortest paths analysis led to the identification of ARG673 as an essential residue for the communication between RdRp and MTase catalytic sites. Mutation of this residue led to changes in the conformational flexibility of the RdRp finger subdomain, which may influence the RdRp catalytic function. These findings serve as a basis for future studies on the mechanism and inhibition of the NS5 dimer for dengue drug discovery.

This qualitative study documents the responses taken by the College of Arts and Sciences (CAS), University of the Philippines (UP) Manila during the COVID-19 pandemic. Utilizing the phenomenological approach, this study narrates the authors' experiences as administrators and faculty members as they responded to the challenges of disruption caused by the pandemic, such as the delivery of Course Packs, digitization of materials, the use of Learning Management Systems, faculty online workshops on remote teaching, and the shift to online transactions. It shows some mechanisms that could be adopted by schools in implementing innovative solutions and strategies to improve the quality of education in the post-pandemic era while some could even be adopted as we shifted to blended learning, bearing in mind the various contexts of our students under the New Normal. The pandemic taught us that these learning tools do not necessarily supplant, but rather supplement, classroom-based instruction.

RNA-dependent RNA-polymerase (RdRp), one of the key enzymes in the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) life cycle, is a recognized druggable target for Coronavirus disease 19 (COVID-19) treatment. Its inhibition has been associated with reduced viral loads in infected individuals. A library of 1562 Philippine Natural Compounds was screened in silico for potential SARS-CoV-2 anti-RdRp activity using a high-throughput virtual screening (VS) approach. Molecular docking experiments and in silico absorption, distribution, metabolism, and excretion (ADME) predictions were used to determine compounds with potential inhibitory capabilities against RdRp. The top three compounds, Vitelignin A (VIT), Vitexoside (VIX), and Cannabifolin C (CAN), were subjected to molecular dynamics (MD) simulations in complex with RdRp, confirming the formation of stable protein-ligand complexes. Overall, these results suggest promising inhibitory capabilities of these three compounds against SARS-CoV-2 RdRp. Their shared presence in extracts of Vitex negundo, a Philippine medicinal plant, warrants further in vitro and in vivo investigation regarding the anti-SARS-CoV-2 activity of its extracts and active components.