Metabolic syndrome (MetS) is a non-communicable disease characterised by a cluster of metabolic irregularities. Alarmingly, the prevalence of MetS in people living with Human Immunodeficiency Virus (HIV) and antiretroviral (ARV) usage is increasing rapidly. This study aimed to look at biochemical mechanisms and epigenetic modifications associated with HIV, ARVs, and MetS. More specifically, emphasis was placed on mitochondrial dysfunction, insulin resistance, inflammation, lipodystrophy, and dyslipidaemia. We found that mitochondrial dysfunction was the most common mechanism that induced metabolic complications. Our findings suggest that protease inhibitors (PIs) are more commonly implicated in MetS-related effects than other classes of ARVs. Furthermore, we highlight epigenetic studies linking HIV and ARV usage to MetS and stress the need for more studies, as the current literature remains limited despite the advancement in and popularity of epigenetics.

The recently discovered coronavirus, known as SARS-CoV-2, is a highly contagious and potentially lethal viral infection that was declared a pandemic by the World Health Organization on March 11, 2020. Since the beginning of the pandemic, an unprecedented number of COVID-19 vaccine candidates have been investigated for their potential to manage the pandemic. Herein, we reviewed vaccine development and the associated research effort, both traditional and forward-looking, to demonstrate the advantages and disadvantages of their technology, in addition to their efficacy limitations against mutant SARS-CoV-2. Moreover, we report repurposed drug discovery, which mainly focuses on virus-based and host-based targets, as well as their inhibitors. SARS-CoV-2 targets include the main protease (M^pro), and RNA-dependent RNA-polymerase (RdRp), which are the most well-studied and conserved across coronaviruses, enabling the development of broad-spectrum inhibitors of these enzymes.

Lately, Spirulina platensis (SP), as an antioxidant, has exhibited high potency in the treatment of oxidative stress, diabetes, immune disorder, inflammatory stress, and bacterial and viral-related diseases. This study investigated the possible protective role of Spirulina platensis against ARV-induced oxidative stress in HepG2 cells. Human liver (HepG2) cells were treated with ARVs ((Lamivudine (3TC): 1.51 µg/mL, tenofovir disoproxil fumarate (TDF): 0.3 µg/mL and Emtricitabine (FTC): 1.8 µg/mL)) for 96 h and thereafter treated with 1.5 µg/mL Spirulina platensis for 24 h. After the treatments, the gene and protein expressions of the antioxidant response pathway were determined using a quantitative polymerase chain reaction (qPCR) and Western blots. The results show that Spirulina platensis decreased the gene expressions of Akt (p < 0.0001) and eNOS (↓p < 0.0001) while, on the contrary, it increased the transcript levels of NRF-2 (↑p = 0.0021), Keap1 (↑p = 0.0002), CAT (↑p < 0.0001), and NQO-1 (↑p = 0.1432) in the HepG2 cells. Furthermore, the results show that Spirulina platensis also decreased the protein expressions of NRF-2 (↓p = 0.1226) and pNRF-2 (↓p = 0.0203). Interestingly, HAART-SP induced an NRF-2 pathway response through upregulating NRF-2 (except for FTC-SP) (↑p < 0.0001), CAT (↑p < 0.0001), and NQO-1 (except for FTC-SP) (↑p < 0.0001) mRNA expression. In addition, NRF-2 (↑p = 0.0085) and pNRF-2 (↑p < 0.0001) protein expression was upregulated in the HepG2 cells post-exposure to HAART-SP. The results, therefore, allude to the fact that Spirulina platensis has the potential to mitigate HAART-adverse drug reactions (HAART toxicity) through the activation of antioxidant response in HepG2 cells. We hereby recommend further studies on Spirulina platensis and HAART synergy.

The prevalence of metabolic syndrome MetS in HIV-infected patients on chronic antiretroviral (ARV) therapy continues to rise rapidly, with an estimated 21% experiencing insulin resistance. The progression of insulin resistance is strongly related to mitochondrial stress and dysfunction. This study aimed to draw links between the singular and combinational use of Tenofovir disoproxil fumarate (TDF), Lamivudine (3TC), and Dolutegravir (DTG) on mitochondrial stress and dysfunction as an underlying mechanism for insulin resistance following a 120 h treatment period using an in vitro system of human liver cells (HepG2). The relative protein expressions of pNrf2, SOD2, CAT, PINK1, p62, SIRT3, and UCP2, were determined using Western blot. Transcript levels of PINK1 and p62 were assessed using quantitative PCR (qPCR). ATP concentrations were quantified using luminometry, and oxidative damage (malondialdehyde (MDA) concentration) was measured using spectrophotometry. The findings suggest that despite the activation of antioxidant responses (pNrf2, SOD2, CAT) and mitochondrial maintenance systems (PINK1 and p62) in selected singular and combinational treatments with ARVs, oxidative damage and reduced ATP production persisted. This was attributed to a significant suppression in mitochondrial stress responses SIRT3 and UCP2 for all treatments. Notable results were observed for combinational treatments with significant increases in pNrf2 (p = 0.0090), SOD2 (p = 0.0005), CAT (p = 0.0002), PINK1 (p = 0.0064), and p62 (p = 0.0228); followed by significant decreases in SIRT3 (p = 0.0003) and UCP2 (p = 0.0119) protein expression. Overall there were elevated levels of MDA (p = 0.0066) and decreased ATP production (p = 0.0017). In conclusion, ARVs induce mitochondrial stress and dysfunction, which may be closely associated with the progression of insulin resistance.

Ubiquitous soil fungi parasitise agricultural commodities and produce mycotoxins. Fumonisin B₂ (FB₂), the structural analogue of the commonly studied Fumonisin B₁ (FB₁), is a neglected mycotoxin produced by several Fusarium species. Mycotoxins are known for inducing toxicity via mitochondrial stress alluding to mitochondrial degradation (mitophagy). These processes involve inter-related pathways that are regulated by proteins related to SIRT3 and Nrf2. This study aimed to investigate mitochondrial stress responses in human kidney (Hek293) cells exposed to FB₂ for 24 h. Cell viability was assessed via the methylthiazol tetrazolium (MTT) assay, and the half-maximal inhibitory concentration (IC₅₀ = 317.4 µmol/L) was estimated using statistical software. Reactive oxygen species (ROS; H₂DCFDA), mitochondrial membrane depolarisation (JC1-mitoscreen) and adenosine triphosphate (ATP; luminometry) levels were evaluated to assess mitochondrial integrity. The relative expression of mitochondrial stress response proteins (SIRT3, pNrf2, LONP1, PINK1, p62 and HSP60) was determined by Western blot. Transcript levels of SIRT3, PINK1 and miR-27b were assessed using quantitative PCR (qPCR). FB₂ reduced ATP production (p = 0.0040), increased mitochondrial stress marker HSP60 (p = 0.0140) and suppressed upregulation of mitochondrial stress response proteins SIRT3 (p = 0.0026) and LONP1 (p = 0.5934). FB₂ promoted mitophagy via upregulation of pNrf2 (p = 0.0008), PINK1 (p = 0.0014) and p62 (p < 0.0001) protein expression. FB₂ also suppressed miR-27b expression (p < 0.0001), further promoting the occurrence of mitophagy. Overall, the findings suggest that FB₂ increases mitochondrial stress and promotes mitophagy in Hek293 cells.