Despite the fact that coronavirus disease 2019 (COVID-19) treatment and management are now considerably regulated, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still one of the leading causes of death in 2022. The availability of COVID-19 vaccines, FDA-approved antivirals, and monoclonal antibodies in low-income countries still poses an issue to be addressed. Natural products, particularly traditional Chinese medicines (TCMs) and medicinal plant extracts (or their active component), have challenged the dominance of drug repurposing and synthetic compound libraries in COVID-19 therapeutics. Their abundant resources and excellent antiviral performance make natural products a relatively cheap and readily available alternative for COVID-19 therapeutics. Here, we deliberately review the anti-SARS-CoV-2 mechanisms of the natural products, their potency (pharmacological profiles), and application strategies for COVID-19 intervention. In light of their advantages, this review is intended to acknowledge the potential of natural products as COVID-19 therapeutic candidates.

Arboviruses are a significant threat to global public health, with outbreaks occurring worldwide. Toll-like receptors (TLRs) play a crucial role in the innate immune response against these viruses by recognizing pathogen-associated molecular patterns and initiating an inflammatory response. Significantly, TLRs commonly implicated in the immune response against viral infections include TLR2, TLR4, TLR6, TLR3, TLR7, and TLR8; limiting or allowing them to replicate and spread within the host. Modulating TLRs has emerged as a promising approach to combat arbovirus infections. This review summarizes recent advances in TLR modulation as a therapeutic target in arbovirus infections. Studies have shown that the activation of TLRs can enhance the immune response against arbovirus infections, leading to increased viral clearance and protection against disease. Conversely, inhibition of TLRs can reduce the excessive inflammation and tissue damage associated with arbovirus infection. Modulating TLRs represents a potential therapeutic strategy to combat arbovirus infections.

The COVID-19 pandemic has caused extensive loss of lives and economic hardship. In response, infectious disease experts and vaccine developers promptly responded by bringing forth candidate vaccines, some of which have been listed in the World Health Organization’s Emergency Use Listing. Notwithstanding the diverse worldwide population genetics, the vaccines thus far developed are generic in nature for use worldwide. Differences in the human leukocyte antigen (HLA) in different populations, variation of the T cell epitopes, and the propensity of SARS-CoV-2 genetic mutations left room for improvement of the vaccines. Here, we discussed the implications of COVID-19 vaccination and SARS-CoV-2 infection by taking into consideration SARS-CoV-2 mutations, T cell epitopes, risk factors, and current platforms of candidate vaccines based on the HLA types that are commonly present in Peninsular Malaysia Chinese, Indian, and Malay populations. The HLA types associated with protection against and susceptibility to severe SARS-CoV-2 infection were identified based on reported case-control and cohort studies. The relevance of including the non-spike SARS-CoV-2 proteins in the future COVID-19 vaccines is also highlighted. This review is meant to trigger researchers to acknowledge the importance of investigating the possible relationships between the HLA haplotype and the SARS-CoV-2 strains circulating in different populations.

In the chronic phase of chikungunya virus (CHIKV) infection, excessive inflammation manifests as incapacitating joint pain and prolonged arthritis. Arthritis resulted from a large influx of infiltrating immune cells driven by pro-inflammatory cytokines and chemokines originating from the toll-like receptor (TLR)-mediated innate antiviral response. This study investigated fisetin’s ability to modulate TLR-mediated antiviral responses against CHIKV in Huh7 cells. The CHIKV inhibitory potential of fisetin was assessed by plaque-forming unit assay, virus yield reduction assay, and bright-field microscopy (cytopathic effect, immunofluorescence). Fisetin’s modulatory potential on TLR-mediated antiviral response was evaluated by immunofluorescence assay (expression of TLR proteins), qRT-PCR (mRNA level of antiviral genes), human cytokine array, and the immunoblotting of key transcription factors. The present study showed fisetin induced the expression of the antiviral genes at an early time-point by promoting the phosphorylation of IRF3 and IRF7. Fisetin reduced excessive inflammatory cytokine responses in CHIKV-infected Huh7 cells by impeding the over-phosphorylation of NF-κB. Fisetin also reduced CHIKV-induced cytopathic effects in CHIKV-infected Huh7 cells. Altogether, our study suggests that fisetin modulates TLR-mediated antiviral responses by affecting the CHIKV-induced inflammatory responses.

Despite the fact that COVID-19 treatment and management are now considerably regulated, SARS-CoV-2 is still one of the leading causes of death in 2022. The availability of COVID-19 vaccines, FDA-approved antivirals, and monoclonal antibodies in low-income countries still poses an issue to be addressed. Natural products, particularly traditional Chinese medicines (TCMs) and medicinal plant extracts (or their active component) have challenged the dominance of drug repurposing and synthetic compound libraries in COVID-19 therapeutics. Abundant resources and excellent antiviral performance make natural products a relatively cheap and easily available alternative for COVID-19 therapeutics. Here, we deliberately review the anti-SARS-CoV-2 mechanisms of the natural products, their potency (pharmacological profiles), and application strategies for COVID-19 intervention. In light of their advantages, this review is intended to acknowledge the potential of natural products as COVID-19 therapeutic candidates.

The study investigated the protective effects of fisetin on chikungunya virus (CHIKV)-induced apoptosis hallmarks in Huh7 cells. Fisetin significantly reduced CHIKV RNA levels and viral infectivity, outperforming Z-VAD-FMK and cisplatin. At 30 µM, fisetin markedly decreased (by > 90%) the number of infectious viral particles at 24 and 48 h post-infection (hpi). Fisetin also hindered CHIKV-induced DNA fragmentation, with the lowest levels observed in CHIKV-infected cells treated with fisetin compared to other treatments. Immunoblot analysis revealed that fisetin inhibited caspase-mediated PARP cleavage and significantly reduced cleaved PARP levels, indicating decreased apoptosis. Additionally, fisetin diminished the expression of cleaved caspase-3 and HSP-27 proteins, while restoring HIF-1α protein levels, suggesting a protective role against CHIKV-induced apoptosis. The study highlights the potential of fisetin as an effective antiviral agent against CHIKV through the modulation of apoptosis and oxidative stress pathways. These findings underscore the therapeutic promise of fisetin for treating CHIKV-induced apoptosis and warrant further investigation to explore its clinical applications and optimize its use in antiviral therapy.