The emergence of the severe acute respiratory syndrome coronavirus-2, responsible for causing corona virus disease 2019 (COVID-19), marked the third time in the twenty-first century when a new, highly pathogenic human coronavirus outbreak has led to an epidemic. The COVID-19 epidemic has emerged in late December 2019 in Wuhan city of China and spread rapidly to other parts of the world. This quick spread of SARS-CoV-2 infection to many states across the globe affecting many people has led WHO to declare it a pandemic on March 11, 2020. In this presentation, we discuss recent updates regarding various therapeutic approaches to combat COVID-19 pandemic according to the biosynthetic source and enlist the major pipeline drugs and traditional medicines that are under trial for COVID-19. Altogether, the information provided in this project dissertation will work as an intellectual groundwork and provides an insight into the ongoing development of various therapeutic agents.

1. Natural Products Against
SARS CoV-2
Presented by-
Apurba Gohain
M.Sc. 4th Semester
Dept. of Chemistry, AUS
Roll- 042119 No-
2010800043
Under supervision of-
Prof. Manobjyoti
Bordoloi
Dept. of chemistry, AUS

2. INTRODUCTION
What is the current pandemic?
• December 2019: a novel (new) coronavirus was identified in Wuhan, China. This virus
has since been named SARS-CoV-2 for severe acute respiratory syndrome
coronavirus 2. It was previously called 2019 novel coronavirus (2019-nCoV).
• The disease caused by SARS-CoV-2 is called COVID-19.
• March 11, 2020: After the disease caused by this coronavirus spread to 114 countries,
the World Health Organization declared it to be a pandemic likely to spread across the
globe.
What is a coronavirus?
• Coronaviruses are a group of viruses that cause several diseases in mammals and
birds.
• In humans, human coronavirus (HCV) causes respiratory infections that are usually mild,
including some cases of the common cold.
• This group of viruses is named for the club-shaped protein spikes
(artificially colored red in the computer model) that protrude from the
viral surface and create the appearance of a “corona” (crown) when
viewed via an electron microscope.

4. Source wise natural product
• Alkaloids
1. Tetrandrine and fangchinoline were shown to have antiviral activity against human coronavirus in vitro. Tetrandrine,
reduced the expression of the S- and N-proteins in MRC-5 lung human cells infected with HCoV-OC43 after infection,
2. Lycorine is extracted from Lycoris radiata plant. L. radiata extract had the strongest inhibitory efficacy in SARS-CoV bioassay guided
fractionation, yielding lycorine as the major bioactive component. Lycorine can produce toxic effects in canine models at low levels (1
mg/kg); more research on this compound as a possible therapeutic candidate is required, and the basis of its antiviral action remained
unclear.
3. The alkaloids indigo, indirubin, indican and sinigrin are the primary components of I. indigotica root. Indigo and
that are versatile. In cell-free and cell-based tests, sinigrin and indigo reduced the cleavage activities of the 3CLpro in a
values in the cell-free assays were 121 μM for sinigrin and 300 μM for indigo.

5. Source wise natural product
• Flavonoids
1. Lin et al. investigated phenolic substances for their inhibitory effects on the SARS-CoV 3CLpro in 2005. In in vitro cell-
hesperetin reduced 3CLpro cleavage activity; the IC50 values of aloeemodin and hesperetin were 132 μM and 60 μM,
2. The production of nucleocapsid (N) protein, which is required for MERS-CoV replication, was reported to suppress after
apoptosis produced by MERS-CoV in vitro.
3. Amentoflavone, a bi-flavonoid derived from Selaginella sinensis, Torreya nucifera, and other medicinal plants, has
respiratory syncytial virus (RSV) in vitro, with a considerable activity against influenza A and B viruses.
4. Myricetin, is a significant flavonoid metabolite. It is found in Ampelopsis japonica plant and had inhibition effect
1.20 μM.
5. Traditional Chinese medicine has long utilised the roots of Scutellaria baicalensis to treat various ailments mainly the
SARS CoV-2.

6. Source wise natural product
• Terpenoids
1. Glycyrrhizin, the active component of liquorice roots, has been reported to possess moderate antiviral activity against SARS-CoV in vitro
with an EC50 of 300 g/mL, however its full mechanism is unclear.
2. Saikosaponins isolated from medicinal plants such as Bupleurum spp., Heteromorpha spp., and Scrophularia scorodonia have been
shown to exhibit anti-inflammatory, immunomodulatory, and antibacterial properties.
3. Betulinic acid (IC50 = 10 μM) and savinin (IC50 = 25 μM) exhibited significant inhibition on 3CLpro.

7. Source wise natural product
• Fatty acids and polyketides- diarylheptanoids
1. Emodin, a key element of the genera Rheum and Polygonum, is the most likely primary ingredient effective for blocking both SARS-CoV
S protein binding to ACE2 and SARS-CoV S protein binding to ACE2.
2. Promazine, an anti-psychotic medication that has been demonstrated to have a substantial effect in suppressing SARS-CoV replication,
also seems to have a similar structure to emodin.
3. PLpro inhibiting potential was observed in an ethanol extract of A. japonica stem bark. There are four diarylheptanoids identified:
platyphyllenone, hirsutenone, platyphylline, oregonin. Using a continuous fluorometric assay, the isolated compounds were evaluated
against SARS-CoV PLpro, and these diarylheptanoids inhibited the PLpro in a dose-dependent manner. The structural-activity
relationship (SAR) of diarylheptanoids revealed that, β -unsaturated carbonyl and catechol groups may play a critical role in SARS-CoV
PLpro suppression by interacting with PLpro nucleophiles.

8. Clinical trials of Natural Product

9. Clinical trials of Natural Product

10. Conclusion and future aspects
• Despite the fact that specific antiviral medications for COVID-19 have yet to be found or approved by the FDA, the use of several
currently existing antiviral agents that target particular steps in the SARS-CoV-2 life cycle could be an alternate therapeutic strategy for
combating the pandemic.
• The development of COVID-19 vaccines is one of the most significant ways for avoiding SARS-CoV-2 infection. So far, a lot of work has
been done, and 33 vaccine candidates have reached clinical trials, with another 143 in the preclinical stage. Despite the tremendous
efforts of companies and researchers throughout the world to develop COVID-19 vaccines, there is still much more to learn that could
aid in the development of better targeted.
• The phase 3 study, on the other hand, will be critical in determining if the vaccine is safe and efficacious in a broad and varied
population. Finally, in order to test vaccine effectiveness, specialised animal models for COVID-19 need be developed.
• In addition, regulatory authorities should guarantee that vaccines are distributed equally to all impacted locations. There is a great need
to develop innovative medicinal countermeasures for both preventive and therapeutic purposes. Because vaccine development can take
12–18 months and drug development can take 10–17 years, repositioning clinically tested therapeutics is one of the most practical
techniques for rapidly identifying and deploying therapeutics for emerging infectious diseases like COVID-19.

11. Acknowledgements
Lastly I want to thank all the faculty members, non teaching staff and
PhD scholars as well as external sir for there immense help and support.
Thank you all.