ABSTRACT
The pandemic outbreak of human coronavirus is a global health concern that affects people of all ages and genders, but there is currently still no effective, approved and potential drug against human coronavirus, as many other coronavirus vaccines have serious side effects while the development of small antiviral inhibitors has gained tremendous attention. For this research, HE was used as a therapeutic target, as the spike protein displays a high binding affinity for both host ACE2 and viral HE glycoprotein. Molecular docking, pharmacophore modelling and virtual screening of 38,000 natural compounds were employed to find out the best natural inhibitor against human coronaviruses with more efficiency and fewer side effects and further evaluated via MD simulation, PCA, DCCR and MMGBSA. The lead compound 'Calceolarioside B' was identified on the basis of pharmacophoric features which depict favorable binding (ΔGbind -37.6799 kcal/mol) with the HE(5N11) receptor that describes positive correlation movements in active site residues with better stability, a robust H-bond network, compactness and reliable ADMET properties. The Fraxinus sieboldiana Blume plant containing the Calceolarioside B compound could be used as a potential inhibitor that shows a higher efficacy and potency with fewer side effects. This research work will aid investigators in the testing and identification of chemicals that are effective and useful against human coronavirus.
ABSTRACT
Natural products have been proven to be the source of many antiviral drugs in the past. History has a bunch of natural products used as traditional medicine, therapies, mixtures, and oils. However, there are many bioactive natural products that need to be evaluated against severe acute respiratory syndrome (SARS-CoV-2) to curb the ongoing pandemic. Several plants and fungal-derived natural products are extensively reported with antiviral activities against SARS-CoV-2. In vitro, preliminary study assays and computational studies revealed several antiviral drugs from natural fungal compounds, including cordycepin isolated from Cordyceps militaris fungi. Polyphenolic compounds isolated from the Broussonetia papyrifera plant showed promising antiviral activity against SARS CoV-2 in in silico studies. Two alkaloid compounds, 10-hydroxyusambarensine and cryptoquindoline isolated from African medicinal plants, inhibited the main protease (Mpro) of SARS CoV-2. At the start of the COVID-19 pandemic, FDA approved the emergency use of chloroquine against SARS CoV-2;chloroquine is a derivative of alkaloid. The development of modern technologies has streamlined the discovery of new drugs from natural products. Gas chromatography–mass spectrometry, infrared radiation, nuclear magnetic resonance, high-performance thin-layer chromatography, and high-performance liquid chromatography and other high output technologies should be available for the structural interpretation and distinguishability of prudent lead molecules
ABSTRACT
Historically, antiviral drugs have been mined from natural products, including polyketides. Polyketides are produced by various plants, microorganisms, and marine organisms as secondary metabolites. They are considered potential therapeutic antiviral compounds to treat the ongoing COVID-19 pandemic. Preciously, polyketides showed significant antiviral activity in vitro against A59 coronavirus: Herpes Simplex Virus 1 (HSV1) and Poliovirus 1. Several polyketide compounds such as adipostatin, bilobol, onnamide, dihydro-onnamide, and pseudo-onnamide showed promising anti-SARS-CoV-2 by binding with main protease (Mpro) that play a key role in the SARS-CoV-2 replication and transcription. Interestingly, according to the molecular dynamic simulation studies, all of them were stable at the Mpro binding site. The preclinical and clinical studies of those compounds/congeners or structurally related modified members are attributed to their flexibility in chemical synthesis. The diverse structural modifications of SARS-CoV-2 can be correlated using the structure–activity relationship (RAS) that will pave the way to develop promising antiviral drugs to reduce the burden of the ongoing COVID-19 pandemic.
ABSTRACT
Saponins, the glycosidic compounds, are the subclass of terpenoids that are exceedingly diverse and largest group of natural products found in plants. Based on the aglycone structure, saponins can be classified as triterpenoid, steroidal, and alkaloidal saponins. Glycyrrhizin is a triterpenoid saponin from the root and rhizome concentrates of Liquorice (Glycyrrhiza glabra). Saponin triterpene glycyrrhizin plays an important role in various activities and applications, including molluscicidal, anti-inflammatory, anti-allergic, antidiabetic, cytotoxic, antitumor, antifungal, antibacterial, antiparasitic, and antiviral. The traditional glycyrrhizin therapy is effective for treating a variety of clinical conditions. Due to the wide range of pharmacological properties, it is commonly used in COVID-19 patients. It inhibits replication of respiratory viruses, causes cytopathological effects, and could be an auxiliary medication for COVID-19 treatment due to its liver-protective properties. This chapter discusses biological and nutraceutical applications of saponins and glycyrrhizin in detail.
ABSTRACT
Vitamins are very important to stay healthy. Taking macronutrients and micronutrients based on the body’s needs prevents us from diseases and can treat them. Vitamins have proven to help deal with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) patients. Vitamin C intake seems to boost immunity. Several studies suggested that vitamin C intake can lower the extent of upper respiratory tract infections (URTIs) besides its other biological functions such as collagen formation and wound healing. Vitamin C works as an anti-oxidant, counteracting the free radicals during an infection. Whenever an infection or disease occurs, it causes the production of reactive oxygen species, or such oxidizing agents help in the inactivation of viruses. Vitamin D is another important micronutrient to treat and prevent URTIs. Commonly, it is recommended for bone and teeth health, but it has also been used for regulating and boosting the immune system. Nutraceutical applications of vitamins are inevitable. Different natural products and foods are good sources of vitamins that can be taken for improved functions of the human body and treatment of diseases. Besides the oral route, vitamins C and D can also be supplied via micro or nanoparticles through other routes. An adequate intake of vitamins positively affects the body in the fight against infections. So, it can also help reduce the severity of illness and morbidity of patients suffering from SARS-CoV-2 infection.
ABSTRACT
Lactoferrin (Lf) is a dynamic and polyfunctional iron-binding protein found in mammalian milk. It possesses antiviral and antibacterial activities, as well as immunological qualities. Researchers have spent much time studying it, and it has lately received attention because of its link to the current coronavirus epidemic. Lf has been revealed to have antiviral properties against coronavirus. It shows that Lf can attach to several of the receptors utilized by coronaviruses, preventing them from entering the body. Other actions of Lf, host receptor angiotensin-converting enzyme-2 (ACE2), and the heparan sulfate proteoglycans (HSPGs), suggest that they may inhibit acute respiratory syndrome coronavirus (SARS-CoV) by binding to host cells. The U.S. Food and Drug Administration (FDA) has determined bovine lactoferrin (bLf) to be safe for human consumption. However, it is not a vitamin, and a study is underway to learn more about Lf’s additional advantages and if past discoveries of this molecule are worth examining. The coronavirus that causes acute respiratory syndrome might be prevented from adhering to host cells by Lf. HSPG and the host receptor ACE2 are significant in other research because Lf may inhibit the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from binding to host cells. Lf (enteric-coated Lf in particular, given its increased bioavailability) may have preventative and curative benefits in the continuing coronavirus disease-2019 (COVID-19) pandemic at some time.
ABSTRACT
The emerging human pathogenic viruses, including the recently emerged severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), have markedly affected the human health and have become a challenge for researchers worldwide. Antibiotic therapy and existing vaccines have reduced the pandemic burden to some extent. However, there is still need for efficient treatment, vaccination, and antiviral agents to control the pandemic. This chapter illustrates the role of bacteriophage in bacterial infections, SARS-COV-2 infected patients, biological activities of phages, phage display method, phages as potential inducers of antiviral immunity, phage-based vaccines, CRISPR and phage-based SARS-CoV-2 vaccines, and possible advantages of phage-based vaccines. It is concluded that phages have considerable breadth in the SARS-CoV-2 pandemic and offer many substantial advantages, such as clearing respiratory bacterial infections, which significantly reduce the burden of mortalities. Phage plays a vital role in triggering antiviral immunity by inducing cytokines such as IFN-α and IL-12. It suggests the role in driving antiviral immunity, triggering TLR3-dependent pattern recognition receptors, inhibiting TNF-driving type I IFN, inducing antiviral immunity through upregulation of the expression of defensin in IL-2, and encouraging a marked upregulation of gene hBD2 that induces virucidal effects, thus playing a key role in anti-SARS-COV-2 immunity. Moreover, phages have been presented as an alternative universal adjuvant-free nano-vaccine platform in which single-phage scaffolds are used to incorporate multiple targets.
ABSTRACT
Scientists provide initial biochemical screenings with recombinant pure severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) main protease (Mpro) to discover prospective lead compounds for future coronavirus disease-19 (COVID-19) therapies because viral proteases, after polymerases, are the most likely targets for antiviral drug development. Quinones attach to cysteine-rich proteins, and COVID-19 central protease contains a Cys145-rich active site. The antiviral action of five embelin-containing plant products from Bangladesh against influenza virus A/Puerto Rico/8/34 (H1N1) MDCK infected cells was examined. All the evidence pointed to scaffold simplification and changing the shikonin naphthazarin nucleus as appropriate approaches for reducing shikonin cytotoxicity as a natural SARS-CoV-2 Mpro inhibitor. As a part of an extensive investigation of the biological properties of naphthoquinones with shikonin as a lead, and to contribute to drug discovery against COVID-19, the present study led to the development of juglone and its enhanced version as potent and effective Mpro inhibitors of SARS-CoV-2, which are promising antiviral medication candidates awaiting further analysis. A fluorescently labeled short peptide carrying a Q-S carboxyl link was used to test the inhibitory activity of synthesized quinones on Mpro of SARS-CoV-2. In the first library of chemicals, the capacity of several natural naphthoquinones and synthetic vitamin K3 was determined to inhibit SARS-CoV-2 Mpro at 10mM. According to a process described in a recent study on the suppression of SARS-CoV-2 Mpro by a methide quinone Celastrol, while attacking the carbonyl carbon, the development of the S–C covalent bond results in a tetrahedral output where the bond develops at the same carbon to which the hydroxy group is connected.