Chapter 1 - Natural products and SARS-CoV-2

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

Chapter 14 - Vitamins and SARS-CoV-2

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.

Chapter 15 - Lactoferrin and SARS-CoV-2

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.

Chapter 12 - Phages and SARS-CoV-2

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.

Chapter 3 - Quinone and SARS-CoV-2

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.

Virtual screening of quinoline derived library for SARS-COV-2 targeting viral entry and replication.

The COVID-19 pandemic infection has claimed many lives and added to the social, economic, and psychological distress. The contagious disease has quickly spread to almost 218 countries and territories following the regional outbreak in China. As the number of infected populations increases exponentially, there is a pressing demand for anti-COVID drugs and vaccines. Virtual screening provides possible leads while extensively cutting down the time and resources required for ab-initio drug design. We report structure-based virtual screening of a hundred plus library of quinoline drugs with established antiviral, antimalarial, antibiotic or kinase inhibitor activity. In this study, targets having a role in viral entry, viral assembly, and viral replication have been selected. The targets include: 1) RBD of receptor-binding domain spike protein S 2) Mpro Chymotrypsin main protease 3) Ppro Papain protease 4) RNA binding domain of Nucleocapsid Protein, and 5) RNA Dependent RNA polymerase from SARS-COV-2. An in-depth analysis of the interactions and G-score compared to the controls like hydroxyquinoline and remdesivir has been presented. The salient results are (1) higher scoring of antivirals as potential drugs (2) potential of afatinib by scoring as better inhibitor, and (3) biological explanation of the potency of afatinib. Further MD simulations and MM-PBSA calculations showed that afatinib works best to interfere with the the activity of RNA dependent RNA polymerase of SARS-COV-2, thereby inhibiting replication process of single stranded RNA virus. Communicated by Ramaswamy H. Sarma.

In silico Potential of Approved Antimalarial Drugs for Repurposing Against COVID-19.

Although the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is wreaking havoc and resulting in mortality and morbidity across the planet, novel treatments are urgently needed. Drug repurposing offers an innovative approach in this context. We report here new findings on the in silico potential of several antimalarial drugs for repurposing against COVID-19. We conducted analyses by docking the compounds against two SARS-CoV-2-specific targets: (1) the receptor binding domain spike protein and (2) the main protease of the virus (MPro) using the Schrödinger software. Importantly, the docking analysis revealed that doxycycline (DOX) showed the most effective binding to the spike protein of SARS-CoV-2, whereas halofantrine and mefloquine bound effectively with the main protease among the antimalarial drugs evaluated in the present study. The in silico approach reported here suggested that DOX could potentially be a good candidate for repurposing for COVID-19. In contrast, to decipher the actual potential of DOX and halofantrine against COVID-19, further in vitro and in vivo studies are called for. Drug repurposing warrants consideration as a viable research and innovation avenue as planetary health efforts to fight the COVID-19 continue.