RESUMO
Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronaviruses 2 (SARS-CoV-2). At present, it is a potentially fatal disease and is of great global public health concern. The pathophysiological understanding of the mode of transmission of COVID-9 and the possible molecular targets are exploring successively to fight against this contagious disease. In this pandemic situation, a large number of countries have been forced to do social distancing and lockdown. The two main pathways of SARS-CoV-2 transmission include (1) droplet infection via the respiratory secretions or by close person to person contact, whereas (2) faecal to oral route transmission is also possible. Thus, the route of entry of SARS-CoV-2 is through the nasal and or oral cavity. Here, we briefly reviewed the current knowledge about COVID-19, considering the potential explanation of the mode of transmission and the different possible molecular drug targets. We highlighted potential approaches to address the antiviral therapy inhibiting the replication of SARS-CoV-2 in the host targeting (a.) RNA-dependent RNA polymerase (b.) serine protease and (c.) proteolytic activation pathways or the cell membrane receptor called the angiotensin- converting enzyme-2 (ACE2). The recently exercised immuno-enhancement therapy to fight against SARS-CoV-2 and treatment strategy using drug combination are also explored here in this review.
Assuntos
Antivirais/química , COVID-19/patologia , Proteínas Virais/química , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Antivirais/metabolismo , Antivirais/uso terapêutico , COVID-19/terapia , COVID-19/transmissão , COVID-19/virologia , Quimioterapia Combinada , Humanos , Imunoterapia , RNA Polimerase Dependente de RNA/química , RNA Polimerase Dependente de RNA/metabolismo , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/metabolismo , Serina Proteases/química , Serina Proteases/metabolismo , Proteínas Virais/metabolismoRESUMO
Panax notoginseng is the most widely used Chinese medicinal herb for the prevention and treatment of ischemic diseases. Its main active ingredients are saponins, including ginsenoside Rb1, ginsenoside Rg1, and notoginsenoside R1, among others. This review provides an up-to-date overview on the pharmacological roles of P. notoginseng constituents in cerebral ischemia. The saponins of P. notoginseng induce a variety of pharmacological effects in the multiscale mechanisms of cerebral ischemic pathophysiology, including anti-inflammatory activity, reduction of oxidative stress, anti-apoptosis, inhibition of amino acid excitotoxicity, reduction of intracellular calcium overload, protection of mitochondria, repairing the blood-brain barrier, and facilitation of cell regeneration. Regarding cell regeneration, P. notoginseng not only promotes the proliferation and differentiation of neural stem cells, but also protects neurons, endothelial cells and astrocytes in cerebral ischemia. In conclusion, P. notoginseng may treat cerebrovascular diseases through multiple pharmacological effects, and the most critical ones need further investigation.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Panax notoginseng/química , Fitoterapia , Saponinas/farmacologia , Saponinas/uso terapêutico , Aminoácidos/toxicidade , Animais , Anti-Inflamatórios , Antioxidantes , Apoptose/efeitos dos fármacos , Barreira Hematoencefálica/patologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/patologia , Isquemia Encefálica/prevenção & controle , Cálcio/metabolismo , Autorrenovação Celular/efeitos dos fármacos , Sequestradores de Radicais Livres , Ginsenosídeos/isolamento & purificação , Humanos , Fármacos Neuroprotetores , Estresse Oxidativo/efeitos dos fármacos , Saponinas/isolamento & purificaçãoRESUMO
Chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) have long been used worldwide as frontline drugs for the treatment and prophylaxis of human malaria. Since the first reported cases in Wuhan, China, in late December 2019, humans have been under threat from coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 (previously known as 2019-nCoV), subsequently declared a pandemic. While the world is searching for expedited approval for a vaccine, which may be only preventative and not a cure, physicians and country leaders are considering several concerted clinical trials suggesting that the age-old antimalarial drugs CQ/HCQ could be a potent therapeutic against COVID-19. Based on accumulating scientific reports, here we highlight the possible modes of action of CQ/HCQ that could justify its use against viral infections. Considering the global health crisis of the COVID-19 pandemic, the option of repurposing old drugs, e.g. CQ/HCQ, particularly HCQ, for the treatment of SARS-CoV-2 infection could be a good choice. CQ/HCQ has diverse modes of action, including alteration of the acidic environment inside lysosomes and late endosomes, preventing endocytosis, exosome release and phagolysosomal fusion, and inhibition of the host cytokine storm. One or more diverse mechanisms might work against viral infections and reduce mortality. As there is no cure for COVID-19, clinical testing of HCQ is urgently required to determine its potency against SARS-CoV-2, as this is the currently available treatment option. There remains a need to find other innovative drug candidates as possible candidates to enter clinical evaluation and testing.