LAUSR

To the Editor, The rapid spread of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2, Coronaviridae family) has infected over 500 million cases, with 6.5 million deaths reported globally since December 2020 (He, Deng, & Li, 2020). The lack of an effective therapy approved by the World Health Organization (WHO) has potentially increased the number of infected individuals worldwide. The respiratory quality of life and the level of pulmonary functional damage can greatly affect the intensity of respiratory failure during COVID-19 infections (Steinbeis et al., 2022). Moreover, COVID-19 infections weaken the immune system resulting in further bacterial or viral infection. Consequently, the virus exposure has caused many patients to develop adverse complications during COVID-19 infections, including pneumonia, acute respiratory distress syndrome, or sepsis (Myall et al., 2021). SARSCoV-2 used angiotensin-converting enzyme 2 (ACE2) as a binding site receptor for the fusion of the viral and host membranes, thereby invading the host cell. Even though the exact mechanism of infection remains largely unidentified, SARS Covid-2 Spike Protein (S1 protein) alone is reported to initiate severe lung disorders (Schroeder & Bieneman, 2022; Suzuki et al., 2021). Therefore, modulating the pulmonary and cardiovascular symptoms of COVID-19 infections could be the key to lowering disease morbidity and mortality. Plant phytochemicals are potent secondary metabolites that include various chemical entities such as polyphenols, flavonoids, steroidal saponins, organ sulfur compounds, and vitamins, with antioxidant, antiinflammatory, anticancer, antibacterial, antifungal, and antiviral properties (George, Dellaire, & Rupasinghe, 2017; Naveen Kumar, George, Suresh, & Kumar, 2013; Rahman, Mathew, Nair, Ramadan, & Vazhappilly, 2021). The most promising small molecules outlined as coronavirus antagonists were found to have a covalently melded cyclic structure, with the majority classified as polyphenols (Mani et al., 2020). With the rise in COVID-19 cases, a surge in research analyzing the plausible use of polyphenols in treating COVID-19 infections has been reported. Few clinical trials have also reported the effectiveness of plant polyphenols in patients with COVID-19. A recent in silico study has shown the effectiveness of 11 phytochemicals, targeting the SARS-CoV-2 essential proteins, including spike glyco-protein (PDB id 5WRG), Nsp9 RNA binding protein (PDBid 6W4B), main protease (PDB id 6Y84), and RNA dependent RNA polymerase (PDB id 6M71), highlighting them as potential drugs against SARS-CoV-2 (Nag et al., 2021). Nigella sativa oil (NSO) is a herbal medicine with known antiviral and immunomodulatory properties. Patients with mild COVID-19 symptoms, when administered with 500 mg of NSO, showed a faster recovery than patients who received standard care, with 63% of patients recovering within 14 days (Koshak et al., 2021). Persian medicine uses herbal formulations based on patients' symptoms and has reported clinical benefits for treating respiratory diseases. When administered with polyherbal formulations along with the standard care, patients with COVID-19 demonstrated a significant reduction of symptoms, including dry cough, fatigue, headache, muscle pain, dyspnea, runny nose, and sputum cough (Karimi et al., 2021). Squalene belongs to a class of triterpenes and has demonstrated antiviral effects and acts by inhibiting viral DNA synthesis. An intravenous injection of 5 mg squalene microemulsion improved the symptoms of COVD-19 within 7 days with significant improvement in lung elevated computed tomography (Ebrahimi et al., 2022). Similarly, in hospitalized-COVID-19 patients, administration of 400–800 g of green propolis extract along with the standard care protocols significantly reduced the length of hospital stay. Interestingly, patients treated with a higher dose of propolis showed a lower incidence of acute lung injury, also identified as a common complication in COVID-19 infections. The mechanism of action of propolis remains unclear; however, quercetin, a component of propolis, has also demonstrated effectiveness against lung cell damage and inhibits cancer cell growth (Silveira et al., 2021). The effect of quercetin on patients with Chronic Obstructive Pulmonary Disease (COPD) with mild-to-severe lung damage showed that patients administrated with 500–2000 mg/day of plant flavonoid limited cell damage and lung inflammation, and rhinovirus-induced lung tumor growth (Han, Barreto, Martinez, Comstock, & Sajjan, 2020). Zataria multiflora (Z) is a traditional medicine widely used to treat respiratory diseases and has potent antiinflammatory and antioxidative effects. Two months of treatment with Zataria multiflora improved the respiratory symptoms in asthmatic patients, as observed by improved pulmonary function tests, and effectively reduced inflammatory cells and a high-sensitivity C-reactive protein (hs-CRP) while increasing IL-10 (Alavinezhad, Ghorani, Rajabi, & Boskabady, 2022). Further, several in vitro and in vivo studies have described the effect of plant polyphenols in lung cells. The alveolar epithelial cells, when treated with the Cannabis Sativa Arbel extract fraction, FCBD, in vitro, showed a significant reduction in COVID-19-related immune response markers, interleukin (IL)-6 and -8. FCBD boosted CD36 and type II receptors for the Fc region of IgG (FcRII) expression and polarization and phagocytosis in macrophages (differentiated KG1 cell line) Received: 22 July 2022 Revised: 10 September 2022 Accepted: 22 September 2022