The novel coronavirus 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a wide range of manifestations. In this regard, growing evidence is focusing on COVID-19 neurological associations; however, there is a lack of established pathophysiological mechanisms and related treatments. Accordingly, a comprehensive review was conducted, using electronic databases, including PubMed, Scopus, Web of Science, and Cochrane, along with the author’s expertize in COVID-19 associated neuronal signaling pathways. Besides, potential phytochemicals have been provided against neurological signs of COVID-19. Considering a high homology among SARS-CoV, Middle East Respiratory Syndrome and SARS-CoV-2, revealing their precise pathophysiological mechanisms seems to pave the road for the treatment of COVID-19 neural manifestations. There is a complex pathophysiological mechanism behind central manifestations of COVID-19, including pain, hypo/anosmia, delirium, impaired consciousness, pyramidal signs, and ischemic stroke. Among those dysregulated neuronal mechanisms, neuroinflammation, angiotensin-converting enzyme 2 (ACE2)/spike proteins, RNA-dependent RNA polymerase and protease are of special attention. So, employing multi-target therapeutic agents with considerable safety and efficacy seems to show a bright future in fighting COVID-19 neurological manifestations. Nowadays, natural secondary metabolites are highlighted as potential multi-target phytochemicals in combating several complications of COVID-19. In this review, central pathophysiological mechanisms and therapeutic targets of SARS-CoV-2 has been provided. Besides, in terms of pharmacological mechanisms, phytochemicals have been introduced as potential multi-target agents in combating COVID-19 central nervous system complications.
【저자키워드】 COVID-19, SARS-CoV-2, Coronaviruses, Pharmacology, NEUROLOGY, nervous system, phytochemicals, signaling pathways, 【초록키워드】 Treatment, Efficacy, coronavirus, SARS-CoV, stroke, Proteins, protease, angiotensin-converting enzyme 2, Novel coronavirus, delirium, Neuroinflammation, Pain, RNA-dependent RNA polymerase, Manifestations, complications, neurological manifestations, therapeutic agent, Central nervous system, mechanisms, respiratory, Evidence, neurological, manifestation, Middle East, therapeutic target, Secondary Metabolite, acute respiratory syndrome, Web of Science, complex, pathophysiological mechanism, homology, complications of COVID-19, pharmacological, combating, lack, caused, conducted, provided, introduced, dysregulated, neurological sign, neuronal, neuronal mechanisms, 【제목키워드】 manifestation, candidate, targeting,