Potential Natural Products Against Respiratory Viruses: A Perspective to Develop Anti-COVID-19 Medicines

Abstract

The emergence of viral pneumonia caused by a novel coronavirus (CoV), known as the 2019 novel coronavirus (2019-nCoV), resulted in a contagious acute respiratory infectious disease in December 2019 in Wuhan, Hubei Province, China. Its alarmingly quick transmission to many countries across the world and a considerable percentage of morbidity and mortality made the World Health Organization recognize it as a pandemic on March 11, 2020. The perceived risk of infection has led many research groups to study COVID-19 from different aspects. In this literature review, the phylogenetics and taxonomy of COVID-19 coronavirus, epidemiology, and respiratory viruses similar to COVID-19 and their mode of action are documented in an approach to understand the behavior of the current virus. Moreover, we suggest targeting the receptors of SARS-CoV and SARS-CoV-2 such as ACE2 and other proteins including 3CLpro and PLpro for improving antiviral activity and immune response against COVID-19 disease. Additionally, since phytochemicals play an essential role in complementary therapies for viral infections, we summarized different bioactive natural products against the mentioned respiratory viruses with a focus on influenza A, SARS-CoV, MERS, and COVID-19.Based on current literature, 130 compounds have antiviral potential, and of these, 94 metabolites demonstrated bioactivity against coronaviruses. Interestingly, these are classified in different groups of natural products, including alkaloids, flavonoids, terpenoids, and others. Most of these compounds comprise flavonoid skeletons. Based on our survey, xanthoangelol E (88), isolated from Angelica keiskei (Miq.) Koidz showed inhibitory activity against SARS-CoV PLpro with the best IC50 value of 1.2 μM. Additionally, hispidulin (3), quercetin (6), rutin (8), saikosaponin D (36), glycyrrhizin (47), and hesperetin (55) had remarkable antiviral potential against different viral infections. Among these compounds, quercetin (6) exhibited antiviral activities against influenza A, SARS-CoV, and COVID-19 and this seems to be a highly promising compound. In addition, our report discusses the obstacles and future perspectives to highlight the importance of developing screening programs to investigate potential natural medicines against COVID-19.

Natural Compounds With Antimicrobial and Antiviral Effect and Nanocarriers Used for Their Transportation

“…For most viral infections, treatment consists of synthetic drugs, including agents such as neuraminidase inhibitors (zanamivir and oseltamivir), channel blockers (amantadine and rimantadine), viral polymerase inhibitors (favipiravir and baloxavir-marboxi), ribavirin, lopinavir-ritonavir, interferon, corticosteroids, and many others ( Omrani et al, 2021 ). Their low efficacy and the development of viral resistance led to an increasing interest in natural products as an important source of antiviral and inhibitory activities.…”

A Multidisciplinary Approach to Coronavirus Disease (COVID-19)

“…In the research in this area, it has been observed that flavonoids, a class of natural polyphenolic compounds commonly found in plants, have a striking potential against the virus. It has been stated that this phytochemical, which has various pharmacological properties, especially antioxidant, antiviral, anti-inflammatory, and antineoplastic activities, exhibits inhibitory properties in almost every step in the viral cycle of SARS-CoV-2 [321]. Baicalin (EC 50 : 12.5 µg/mL), a bioactive glycosylated flavonoid found especially in Citrus species, while showing the most effective antiviral activity as an ACE2 inhibitor against the prototype SARS virus growing in the fetal Rhesus Kidney-4 (FRhK-4) cell line [322,323], an in silico study made for TMPRSS2 of SARS-CoV-2 has also shown that it acted as a natural inhibitor.…”

“…Furthermore, in an in vitro study, it was specified that contents of capsules in traditional Chinese medicine (Lianhua Qingwen) showed antiviral and anti-inflammatory activity by inhibiting SARS-CoV-2 replication. Again, when the same capsules are combined with Ribavirin, Lopinavir/Ritonavir, and Umifenovir basic therapy, and administered to patients infected with SARS-CoV-2, it has been reported that many important symptoms are overcome in a remarkably short time [321]. When we look at the evidence we have, there are many promising but disorganized and unsubstantiated studies on natural products.…”

Potential SARS-CoV-2 3CLpro inhibitors from chromene, flavonoid and hydroxamic acid compound based on FRET assay, docking and pharmacophore studies

“…Instead of synthetic compound being developed, natural products should be one alternative to speed up the discovery of SARS-CoV-2 antiviral agent [20] . Unfortunately, to the best of our knowledge, there has been less studies reporting compounds from natural products having in vitro / in vivo activity against the virus.…”