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Review
. 2021 Jan 20:11:621099.
doi: 10.3389/fphar.2020.621099. eCollection 2020.

Targeting Neurological Manifestations of Coronaviruses by Candidate Phytochemicals: A Mechanistic Approach

Sajad Fakhri  1 , Sana Piri  1 , Mohammad Bagher Majnooni  2 , Mohammad Hosein Farzaei  1 , Javier Echeverría  3
Affiliations
Review

Targeting Neurological Manifestations of Coronaviruses by Candidate Phytochemicals: A Mechanistic Approach

Sajad Fakhri et al. Front Pharmacol. .

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; coronaviruses; nervous system; neurology; pharmacology; phytochemicals; signaling pathways.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Chemical structures of selected polyphenols/flavonoids with the potential of being used against COVID-19 neurological manifestations.
FIGURE 2
FIGURE 2
Chemical structures of selected alkaloids/terpenes/quinones with the potential of being used against COVID-19 neurological manifestations.
FIGURE 3
FIGURE 3
The neurological manifestations in COVID-19, related pathophysiological mechanisms, and promising role of phytochemicals. COVID-19: coronavirus 2019, PLpro: papain-like protease, RdRP: RNA-dependent RNA polymerase, SARS-CoV-2: severe acute respiratory syndrome coronavirus 2, TMPRSS2: transmembrane protease, serine 2, 3CLpro: 3-chymotrypsin-like cysteine protease.
See this image and copyright information in PMC

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