INTRODUCTION:

COVID 19 has become a global pandemic aggregated throughout the earth. It is transforming the entire human race to death. Within 100 days, thousands of people lay dead with no respect for gender or race or even geographical ethnicity. In general, SARS-CoV-2(CoVID19) is one of the seven human coronaviruses. On Microscopic assessment, found to be a single-stranded RNA virus just like a respiratory syncytial virus. Retrospectively, SARS in 2002 and MERS in 2012 have similar clinical effects like fever, sore throat, cough, and running nose and pneumonia, COVID in 2020 representing the same scenario.

Pathogenesis of COVID:

This novel coronavirus belongs to coronoviridae family just like SAR-COV 2 (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome), of beta-coronoviridae which constitute about 30% upper respiratory infections. NIH funded Researcher stepping towards treating and prevention measures created a first atomic-scale map for developing a vaccine against COVID-19¹. Where the spike protein appendage is responsible to contact with human mucus epithelium that binds to ACE-II receptor. Coronaviruses use homotrimers of the spike (S) glycoprotein which is class 1 viral fusion protein consisting of 1,300 amino acids to form a single polypeptide chain precursor to promote host attachment and fusion of the viral and cellular membranes for entry. It is the main antigen present at the viral surface and is the target of neutralizing antibodies during the infection. For many coronaviruses, S is processed by host proteases to generate two subunits, designated S1 and S2, which remain non-covalently bound in the pre-fusion conformation. The N-terminal (S1) subunit comprises four β-rich domains, designated A, B, C, and D, with domain A or B acting as receptor-binding domains (RBD) in different coronaviruses and fusion peptide which on irreversible confirmation changes leads to heptad replication and release of the viral genome into host cells².

Mortality rate:

In general, geriatrics group is significantly determined in to young (65-74) middle (75-84) and old (85 and >). In addition, the elderly population have high rate of morbidly rate with cardiovascular diseases and cancer, osteoporosis, high cholesterol, dementia etc. Although this is due to decline in functionality of cell and even low hygiene condition. According to united nations, world population prospectus (2010), India has about 80 million and china with 160 millions of elderly population (>65 & old even).

Moving to pandemic i.e., SAR-CoV-2, mortality rate is high in elderly population 36.5% in >70 years and 34.9% in 51-70 years and fatality rate is greater in male that of females represented in below table³

Table 1: Correlating fatality rate with co-morbid conditions

Co-morbid conditions

Fatality rate (%)

Yes

Cardiovascular disease 10.5

Diabetes 7.3

Chronic respiratory disease 6.3

Hypertension 6.0

Cancer 5.6

0.9

Immunosenescence:

As on ageing, cell’s ability of regeneration and regulation may gradually decline which is similar in all the systems for e.g.: in immune system,

· B and T cell generation and proliferation is gradually reduced

· Distinguish between self and foreign antigen

· Increase in pro-inflammatory response

· Minimized antigen–antibody complex, results in aggregation of antigens

Similarly in lungs, alveoli count is reduced and elasticity of lungs gradually decline with low oxygen absorption and inability to expel debris and mucus^4,5. On focusing, geriatrics population are progress to immunization to tackle pneumonia, influenza etc. Immunization schedule for adults as follows: Table :2

Table 2: Vaccination, disease and their dose⁶.

Vaccine	Disease	Dosing schedule
Influenza	Seasonal flu (influenza)	1 dose annually
Tdap	Tetanus, diphtheria, and pertussis	1 dose tdap then tdap booster for every 10 yrs
Shingles’ vaccine	Shingles	1 or 2 doses
Pneumococcal polysaccharide vaccine (PPSV23)	Serious pneumococcal disease, including meningitis and bloodstream infection	1 or 2 doses depending on indication
Pneumococcal conjugate vaccine (PCV13)	Serious pneumococcal disease and pneumonia	1 dose

Table 3: Target proteins (SARS-CoV-2). ⁷

Host pathway in proteome interaction screen	Corresponding SARS-CoV-2 proteins interacting with host pathway
DNA replication	Nsp1
Epigenetic and gene expression regulators	Nsp5, Nsp8, Nsp13, E
Vesicle trafficking	Nsp6, Nsp7, Nsp10, Nsp13, Nsp15, Orf3a, E, Orf8
Lipid modification	Spike
RNA processing and regulation	Nsp8, N
Ubiquitin ligases	Orf10
Host signaling	Nsp8, Nsp13, N, Orf9b
Nuclear transport machinery	Nsp9, Nsp15, Orf6
Cytoskeleton	Nsp1, Nsp13
Mitochondria	Nsp4, Nsp8, Orf9c
Extracellular matrix	Nsp9

Table 4: Existing drug classes targeting identified COVID19 host pathways. ⁷

Bromodomain (BRD) inhibitors

CK2 inhibitors

HDAC1/2 inhibitors

mTOR inhibitors

Nuclear export inhibitors

Sigma factor inhibitors

NEK9 inhibitors

CEP250 inhibitor

PPIAIMPDH2 modulator

Translation inhibitors

Viral transcription inhibitors

ACE inhibitors

Serine protease I inhibitors

Inhibitors of mitochondrial translation

Table 5: Some antiviral phytochemicals.⁸

Sl. No.	Phytochemicals	Plant (part)
1	Baicalin	Scutellaria baicalensis (roots)
2	Chalcones	Glycyrrhiza inflate (roots)
3	Dammarenolic acid	Aglaia sp. (bark)
4	Decanoylphorbol-13 acetate	Croton mauritianus (leaves)
5	Excoecarianin, Loliolide	Phyllanthus urinaria (whole plant)
6	Honokiol	Magnolia tree (roots, bark)
7	Jubanines	Ziziphus jujuba (roots)
8	Limonoids	Swietenia macrophylla (stem)
9	Oleanane	Camellia japonica (flowers)
10	Quercetin	Embelia ribes (seeds)
11	Saikosaponins	Bupleurum kaoi (roots)
12	Sennoside A	Rheum palmatum (roots)
13	Silvestrol	Aglaia foveolata (leaves, bark)
14	SJP-L-5	Schisandra micrantha (roots)
15	Spiroketalenol	Tanacetum vulgare (rhizome)
16	Swerilactones	Swertia mileensis (whole plant)
17	Xanthohumol	Humulus lupulus (whole plant)
18	Oxyresveratrol	Artocarpus lakoocha
19	Saikosaponin B2	Bupleurum kaoi (Root)
20	Tangeretin and nobiletin	Citrus reticulate (Pericarps)
21	Jatrophane ester	Euphorbia amygdaloides spp. and semiperfoliata (Whole plant)
22	Glycyrrhizic acid	Glycyrrhiza radix (Roots)
23	Quercetin 3-rhamnoside	Houttuynia cordata (Aerial parts)
24	Samarangenin B	Limonium sinense (Root)
25	LPRP-Et-97543	Liriope platyphylla (Root)
26	Tetranortriterpenoid 1-cinnamoyl- 3, 11-dihydroxymeliacarpin (CDM)	Melia azedarach L. (Leaves)
27	Lignin–carbohydrate complex	Prunella vulgaris (Fruit spikes)
28	Pterocarnin A	Pterocarya stenoptera (Bark)
29	Chalepin and pseudane IX	Ruta angustifolia (Leaves)
30	Manassantin B	Saururus chinensis (Root)
31	Dicaffeoylquinic acids	Schefflera heptaphylla (Leaf stalks)
32	Scopadulcic acid B	Scoparia dulcis L. (Whole plant)
33	5,7,4' trihydroxy-8- methoxyflavone (F36)	Scutellaria baicalensis (Root)
34	Naringin	Grape and orange (skin)
35	Myricetin	Myrica cerifera
36	Inophyllum_B	Calophyllum inophyllum
37	Inophyllum_P	Calophyllum inophyllum
38	Pericalline	Catharanthus roseus / C. lanceus
39	Chrysophanic acid	Dianella longifolia
40	Nordihydroguaiaretic acid	Larrea divaricata
41	Retrojusticidin B	Phyllanthus myrtifolius
42	Emodin	Rheum sp. and Polygonum sp.
43	Gingerol	Zingiberis rhizome
44	Anthraquinone	Dianella longifolia
45	Methyl rosmarinate	Hyptis atrorubens Poit
46	Licoleafol	Glycyrrhiza uralensis
47	Amaranthin	Amaranthus tricolor
48	Calceolarioside B	Fraxinus sieboldiana
49	Papaverine	Papaver somniferum
50	Biopterin	Crithidia fasciculata
51	Buchapine	Euodia roxburghiana
52	Caribine	Hymenocallis arencola
53	Lycorine	Clivia miniata
54	Fisetin	Rhus spp.
55	Morin	Prunus dulcis, Chlorophora tinctoria, Psidium guajava etc.
56	Luteolin	Matricaria inodora L.
57	Rutin	Fagopyrum esculentum
58	Taxifolin	Acacia catechu
59	Oleanolic acid	Prosopis glandulosa
60	Betulinic acid	Syzigium claviflorum

Sl. No.	Plant	Mode of action
1	Phenolic plant compounds andExtract of roots of Isatis indigotica	inhibits SARS-3CLpro enzyme activity
2	Flavanoid Baicalin from Scutellaria baicalensis	inhibits Angiotensin Converting Enzyme
3	Water extract of Houttuynia cordata	inhibit the activity of viral SARS-3CLpro Block viral RNA-dependent RNA polymerase activity
4	Glycyrhizzin from the liquorice roots Affects various cellular signalling	Affects various cellular signalling pathways
5	Mannose-specific plant lectins derived from Galanthus nivalis, Hippeastrum hybrid and Allium interaction porrum	Inhibition of virus replication at an early stage by blocking S- receptor
6	Reserpine derived from various species of Rauwolfia Scutellarein and myricetin	inhibits replication of SARS-CoV
7	Escin from horsechestnut Extracts of Rheum palmatum IFlavonoids (herbacetin, pectolinarin, epigallocatechin gallate, rhoifolin, quercetin, and gallocatechin gallate)	inhibit SARS-3CLpro activity
8	Quercetin and TSL-1 from leaves of Toona sinensis Roem	Inhibit the cellular entry of virus
9	Luteolin from Veronicalina riifolia	Binds with surface spike protein thus interrupting with membrane fusion of SARS-CoV
10	Lycorine extracted from Lycoris radiate	unclear
11	Emodin derived from genus Rheum and Polygonum	Blocks 3a ion channel inhibiting HCoV-OC43 triggered apoptosis
12	Chloroquine	Decrease Lysosomal autophagy preventing entry of virus

Table 4: Existing drug classes targeting identified COVID19 host pathways. 7

Table 5: Some antiviral phytochemicals.8

Table 6: Some antiviral mechanism by medicinal plants/phytochemicals.9

Table 4: Existing drug classes targeting identified COVID19 host pathways. ⁷

Table 5: Some antiviral phytochemicals.⁸

Table 6: Some antiviral mechanism by medicinal plants/phytochemicals.⁹