Synergistic action of organophosphates and COVID-19 on inflammation, oxidative stress, and renin-angiotensin system can amplify the risk of cardiovascular maladies.

Organophosphates (OPs) are ubiquitous environmental contaminants, widely used as pesticides in agricultural fields. In addition, they serve as flame-retardants, plasticizers, antifoaming or antiwear agents in lacquers, hydraulic fluids, and floor polishing agents. Therefore, world-wide and massive application of these compounds have increased the risk of unintentional exposure to non-targets including the human beings. OPs are neurotoxic agents as they inhibit the activity of acetylcholinesterase at synaptic cleft. Moreover, they can fuel cardiovascular issues in the form of myocardities, cardiac oedema, arrhythmia, systolic malfunction, infarction, and altered electrophysiology. Such pathological outcomes might increase the severity of cardiovascular diseases which are the leading cause of mortality in the developing world. Coronavirus disease-19 (COVID-19) is the ongoing global health emergency caused by SARS-CoV-2 infection. Similar to OPs, SARS-CoV-2 disrupts cytokine homeostasis, redox-balance, and angiotensin-II/AT1R axis to promote cardiovascular injuries. Therefore, during the current pandemic milieu, unintentional exposure to OPs through several environmental sources could escalate cardiac maladies in patients with COVID-19.

In Silico Analysis Reveals the Inhibitory Potential of Madecassic Acid against Entry Factors of SARS-CoV-2.

Coronavirus disease 19 (COVID-19) is the ongoing global health emergency caused by SARS-CoV-2 infection. The virus is highly contagious, affecting millions of people worldwide. SARS-CoV-2, with its trimeric spike glycoprotein, interacts with the angiotensin-converting enzyme 2 (ACE2) receptor and other co-receptors like basigin to invade the host cell. Moreover, certain host proteases like transmembrane serine proteases, furin, neuropilin 1 (NRP1), and endosomal cathepsins are involved in the priming of spike glycoproteins at the S1/S2 interface. This is critical for the entry of viral genome and its replication in the host cytoplasm. Vaccines and anti-SARS-CoV-2 drugs have been developed to overcome the infection. Nonetheless, the frequent emergence of mutant variants of the virus has imposed serious concerns regarding the efficacy of therapeutic agents, including vaccines that were developed for previous strains. Thus, screening and development of pharmaceutical agents with multi-target potency could be a better choice to restrain SARS-CoV-2 infection. Madecassic acid (MDCA) is a pentacyclic triterpenoid found in Centella asiatica. It has multiple medicinal properties like anti-oxidative, anti-inflammatory, and anti-diabetic potential. However, its implication as an anti- SARS-CoV-2 agent is still obscure. Hence, in the present in silico study, the binding affinities of MDCA for spike proteins, their receptors, and proteases were investigated. Results indicated that MDCA interacts with ligand-binding pockets of the spike receptor binding domain, ACE2, basigin, and host proteases, viz. transmembrane serine proteinase, furin, NRP1, and endosomal cathepsins, with greater affinities. Moreover, the MDCA-protein interface was strengthened by prominent hydrogen bonds and several hydrophobic interactions. Therefore, MDCA could be a promising multi-target therapeutic agent against SARS-CoV-2 infection.

Synergistic action of organophosphates and COVID-19 on inflammation, oxidative stress, and renin-angiotensin system can amplify the risk of cardiovascular maladies

Organophosphates (OPs) are ubiquitous environmental contaminants, widely used as pesticides in agricultural fields. In addition, they serve as flame-retardants, plasticizers, antifoaming or antiwear agents in lacquers, hydraulic fluids, and floor polishing agents. Therefore, world-wide and massive applications of these compounds have increased the risk of unintentional exposure to non-targets including the human beings. OPs are neurotoxic agents as they inhibit the activity of acetylcholine esterase at synaptic cleft. Moreover, they can fuel cardiovascular issues in the form of myocardities, cardiac oedema, arrhythmia, systolic malfunction, infarction, and altered electrophysiology. Such pathological outcomes might increase the severity of cardiovascular diseases which are the leading cause of mortality in the developing world. Coronavirus disease-19 (COVID-19) is the ongoing global health emergency caused by SARS-CoV-2 infection. Similar to OPs, SARS-CoV-2 disrupts cytokine homeostasis, redox-balance, and angiotensin-II/AT1R axis to promote cardiovascular injuries. Therefore, during the current pandemic milieu, unintentional exposure to OPs through several environmental sources could escalate cardiac maladies in patients with COVID-19. Graphical Unlabelled Image

Understanding the cross-talk between mediators of infertility and COVID-19.

COVID-19 is the ongoing health emergency affecting individuals of all ages around the globe. Initially, the infection was reported to affect pulmonary structures. However, recent studies have delineated the impacts of COVID-19 on the reproductive system of both men and women. Hence, the present review aims to shed light on the distribution of SARS-CoV-2 entry factors in various reproductive organs. In addition, impacts of COVID-19 mediators like disrupted renin angiotensin system, oxidative stress, cytokine storm, fever, and the mental stress on reproductive physiology have also been discussed. For the present study, various keywords were used to search literature on PubMed, ScienceDirect, and Google Scholar databases. Articles were screened for relevancy and were studied in detail for qualitative synthesis of the review. Through our literature review, we found a multitude of effects of COVID-19 mediators on reproductive systems. Studies reported expression of receptors like ACE-2, TMPRSS2, and CD147 in the testes, epididymis, prostrate, seminal vesicles, and ovarian follicles. These proteins are known to serve as major SARS-CoV-2 entry factors. The expression of lysosomal cathepsins (CTSB/CTSL) and/ neuropilin-1 (NRP-1) are also evident in the testes, epididymis, seminal vesicles, fallopian tube, cervix, and endometrium. The binding of viral spike protein with ACE-2 was found to alter the renin-angiotensin cascade, which could invite additional infertility problems. Furthermore, COVID-19 mediated cytokine storm, oxidative stress, and elevated body temperature could be detrimental to gametogenesis, steroidogenesis, and reproductive cycles in patients. Finally, social isolation, confinement, and job insecurities have fueled mental stress and frustration that might promote glucocorticoid-mediated subnormal sperm quality in men and higher risk of miscarriage in women. Hence, the influence of COVID-19 on the alteration of reproductive health and fertility is quite apparent.

Immunotoxic role of organophosphates: An unseen risk escalating SARS-CoV-2 pathogenicity.

Consistent gathering of immunotoxic substances on earth is a serious global issue affecting people under pathogenic stress. Organophosphates are among such hazardous compounds that are ubiquitous in nature. They fuel oxidative stress to impair antiviral immune response in living entities. Aside, organophosphates promote cytokine burst and pyroptosis in broncho-alveolar chambers leading to severe respiratory ailments. At present, we witness COVID-19 outbreak caused by SARS-CoV-2. Infection triggers cytokine storm coupled with inflammatory manifestations and pulmonary disorders in patients. Since organophosphate-exposure promotes necroinflammation and respiratory troubles hence during current pandemic situation, additional exposure to such chemicals can exacerbate inflammatory outcome and pulmonary maladies in patients, or pre-exposure to organophosphates might turn-out to be a risk factor for compromised immunity. Fortunately, antioxidants alleviate organophosphate-induced immunosuppression and hence under co-exposure circumstances, dietary intake of antioxidants would be beneficial to boost immunity against SARS-CoV-2 infection.