Therapeutic Potential of Bioactive Compounds from Edible Mushrooms to Attenuate SARS-CoV-2 Infection and Some Complications of Coronavirus Disease (COVID-19)

Abstract

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly infectious positive RNA virus, has spread from its epicenter to other countries with increased mortality and morbidity. Its expansion has hampered humankind's social, economic, and health realms to a large extent. Globally, investigations are underway to understand the complex pathophysiology of coronavirus disease (COVID-19) induced by SARS-CoV-2. Though numerous therapeutic strategies have been introduced to combat COVID-19, none are fully proven or comprehensive, as several key issues and challenges remain unresolved. At present, natural products have gained significant momentum in treating metabolic disorders. Mushrooms have often proved to be the precursor of various therapeutic molecules or drug prototypes. The plentiful bioactive macromolecules in edible mushrooms, like polysaccharides, proteins, and other secondary metabolites (such as flavonoids, polyphenols, etc.), have been used to treat multiple diseases, including viral infections, by traditional healers and the medical fraternity. Some edible mushrooms with a high proportion of therapeutic molecules are known as medicinal mushrooms. In this review, an attempt has been made to highlight the exploration of bioactive molecules in mushrooms to combat the various pathophysiological complications of COVID-19. This review presents an in-depth and critical analysis of the current therapies against COVID-19 versus the potential of natural anti-infective, antiviral, anti-inflammatory, and antithrombotic products derived from a wide range of easily sourced mushrooms and their bioactive molecules.

Keywords: COVID-19 therapy; SARS-CoV-2; bioactive molecules anti-COVID-19; medicinal mushrooms; virus–host interaction.

Figure 1

(A). Structure of SARS-CoV-2. This figure was created in BioRender with a paid subscription (agreement number: FU25P9V166). (B). Schematic diagram showing the mechanism of SARS-CoV-2 infection. The process starts with the attachment of the viral spike (S) protein to the host angiotensin converting enzyme 2 (ACE2) receptor and the facilitation of cellular entry by host cell protease (TMPRSS2). The endocytosed SARS-CoV-2 releases the virus into the host cell, and viral RNA is translated into viral replicase. The replicase polyproteins are subsequently cleaved into non-structural proteins (NSPs). The enzyme replicase uses a positive-strand RNA genome template to generate full-length negative-strand RNA. The RNA-dependent RNA polymerase (RdRp) transcribes a series of sub-genomic mRNAs that are translated into viral structural proteins (spike (S), envelope (E), nucleocapsid (N), membrane (M), and accessory protein (A)). The positive-strand RNA and viral proteins are assembled in the endoplasmic reticulum (ER) and Golgi. The newly formed virus particles are released from the infected cells by exocytosis and are ready to infect other healthy cells. This figure was created in BioRender with a paid subscription (agreement number: HR25PB901A).

Figure 1

(A). Structure of SARS-CoV-2. This figure was created in BioRender with a paid subscription (agreement number: FU25P9V166). (B). Schematic diagram showing the mechanism of SARS-CoV-2 infection. The process starts with the attachment of the viral spike (S) protein to the host angiotensin converting enzyme 2 (ACE2) receptor and the facilitation of cellular entry by host cell protease (TMPRSS2). The endocytosed SARS-CoV-2 releases the virus into the host cell, and viral RNA is translated into viral replicase. The replicase polyproteins are subsequently cleaved into non-structural proteins (NSPs). The enzyme replicase uses a positive-strand RNA genome template to generate full-length negative-strand RNA. The RNA-dependent RNA polymerase (RdRp) transcribes a series of sub-genomic mRNAs that are translated into viral structural proteins (spike (S), envelope (E), nucleocapsid (N), membrane (M), and accessory protein (A)). The positive-strand RNA and viral proteins are assembled in the endoplasmic reticulum (ER) and Golgi. The newly formed virus particles are released from the infected cells by exocytosis and are ready to infect other healthy cells. This figure was created in BioRender with a paid subscription (agreement number: HR25PB901A).

Figure 2

Structure of β-(1 → 3)-glucan backbones with β-(1 → 6)-glucosyl side-branching units.

Figure 3

Structure of (A) applanoxidic acid G, (B) ergosta-7, 22-diene-3b-ol, (C) lucidadiol, (D) lucialdehyde B, (E) sesquiterpenoid.

Figure 4

Structure of (A) colossolactone G, (B) heliantriol F, (C) ergosterol, (D) colossolactone VIII, (E) velutin, and (F) colossolactone E.

Figure 5

Patients suffering from acute COVID-19 showed an inflammatory or cytokine storm (CS) in the lung with an immoderately uncontrolled delivery of pro-inflammatory cytokines and the effect of naturally derived compounds during inflammation. This figure was created in BioRender with a paid subscription (agreement number: DH25PFBESY).

Figure 6

Structure of (A) cordycepin and (B) oligoporin A.