PMC:7755033 / 2086-14590 JSONTXT 3 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T21 0-2 Sentence denotes 1.
T22 4-16 Sentence denotes Introduction
T23 17-130 Sentence denotes As per the World Health Organization (WHO), viral diseases are on the rise posing serious public health concerns.
T24 131-345 Sentence denotes Over the last twenty years, numerous viral epidemics such as the Severe Acute Respiratory Syndrome (SARS) in 2002–2003, H1N1 influenza in 2009 and Middle East Respiratory Syndrome (MERS) in 2012 have been reported.
T25 346-545 Sentence denotes Wuhan, the sprawling capital of Central China’s Hubei province very recently witnessed ‘pneumonia of unknown etiology’ that was first reported to the WHO Country Office in China on December 31, 2019.
T26 546-687 Sentence denotes The causal agent coronavirus belonging to the family coronaviridae are enveloped viruses which are divided into four genera (α, β, γ, and δ).
T27 688-870 Sentence denotes The SARS-CoV-2 virus (formerly designated as COVID-19) belonging to the class of β-coronaviruses is supposed to have evolved from bats and thereafter, spread like wildfire worldwide.
T28 871-1144 Sentence denotes A total of 43,825,003 confirmed cases of COVID-19 and 1,165,289 deaths have been registered round the globe, whereas in India the confirmed cases has reached to 7,946,429 with 119,535 deaths as of October 27, 2020 (https://www.worldometers.info/coronavirus/country/india/).
T29 1145-1255 Sentence denotes Coronaviruses are a large family of single stranded RNA (ssRNA) viruses ranging from 60 to 140 nm in diameter.
T30 1256-1442 Sentence denotes Under the electron microscope, they appear to possess spike like projections present on the surface giving it a crown like appearance, hence named ‘coronaviruses’ (Richman et al., 2016).
T31 1443-1587 Sentence denotes SARS-CoV-2 virus spreads faster than its two predecessors (SARS-CoV and MERS-CoV), but has a lower fatality rate though it is highly contagious.
T32 1588-1641 Sentence denotes Coronavirus possesses four main structural proteins :
T33 1642-1754 Sentence denotes Spike (S) protein, membrane (M) protein, envelope (E) protein and nucleocapsid (N) protein (Bosch et al., 2003).
T34 1755-1935 Sentence denotes Published literature has tracked the onset of symptoms which include a pandemic of cases with pneumonia, unexplained lower respiratory tract infections and multi-organ dysfunction.
T35 1936-1992 Sentence denotes On the other hand, many reported cases are asymptomatic.
T36 1993-2072 Sentence denotes SARS-CoV-2 has become one of the major disease pathogens in emerging outbreaks.
T37 2073-2220 Sentence denotes Intense co-operative worldwide efforts and aggressive isolation measures have more or less led to a progressive decline in the number of incidents.
T38 2221-2374 Sentence denotes The political and health authorities are making an extraordinary effort to halt the shock wave which is seriously challenging the health system globally.
T39 2375-2503 Sentence denotes Currently, therapeutic options are limited and preventive attempts to minimize social transmission are our best defence weapons.
T40 2504-2633 Sentence denotes Researchers are working diligently to find novel and/or repurposed therapeutic options to prevent and treat this global pandemic.
T41 2634-3159 Sentence denotes In this process, they have laid down three strategies , the first includes testing of existing broad-spectrum antiviral drugs (Chan et al., 2013), the second strategy is to use molecular dynamics tools to screen for natural molecules effective as therapeutic and preventive drugs (de Wilde et al., 2014; Dyalla et al., 2014), and third strategy includes the direct utilization of genomic information and pathological symptoms of different mutated coronaviruses to develop new targeted drugs from scratch (Zumla et al., 2016).
T42 3160-3361 Sentence denotes Till date, research has identified more than 30 therapeutic agents, including natural products, allopathic drugs and traditional Chinese medicines which could potentially be effective against COVID-19.
T43 3362-3713 Sentence denotes For initial treatment of COVID-19, the People's Republic of China National Health Commission (NHC) has included antiviral agents including interferon α (IFN-α), lopinavir/ritonavir, chloroquine phosphate, ribavirin and arbidol in the revised edition of the guidelines for the prevention, diagnosis and treatment of novel coronavirus-induced pneumonia.
T44 3714-3913 Sentence denotes Combinations of protease inhibitor(s) lopinavir/ritonavir for the treatment of COVID-19 infected patients have been evaluated which have been used previously to treat HIV patients (Liu et al., 2020).
T45 3914-4280 Sentence denotes In several animal models, including non-human primates (Fouchier et al., 2003; Kuiken et al., 2003; McAuliffe et al., 2004; Rowe et al., 2004), ferrets (Martina et al., 2003), mice (Glass et al., 2004; Hogan et al., 2004) and Syrians hamsters (Roberts et al., 2005), experimental infections with SARS-CoV have been found to cause severe respiratory tract infections.
T46 4281-4525 Sentence denotes Several antiviral therapies have been identified for human pathogenic CoVs including synthetic inhibitors of neuraminidase, nucleoside analogs, remdesivir, tenofovir disoproxil (TDF), umifenovir (arbidol) and lamivudine (3TC) (Li et al., 2005).
T47 4526-4668 Sentence denotes Studies involving identification of cellular receptors that facilitate the binding and entry of human associated coronaviruses have been done.
T48 4669-4911 Sentence denotes Angiotensin I-converting enzyme 2 (ACE2) is a membrane bound aminopeptidase expressed in renal, cardiovascular, vascular and testicular tissue, as well as the small intestine (Donoghue et al., 2000; Hamming et al., 2004; Harmer et al., 2002).
T49 4912-5063 Sentence denotes It has been shown to be a co-receptor for viral entry of SARS-CoV-2 with increasing evidence that it has a significant role in SARS-CoV-2 pathogenesis.
T50 5064-5247 Sentence denotes Therefore, targeting the human ACE2 receptor might block the entry and the subsequent pathophysiology of the virus and is one of the premises of the present study (Zhou et al., 2020).
T51 5248-5554 Sentence denotes SARS-CoV-2 entry into host cells is mediated by transmembrane spike(S) like glycoprotein that causes neutralization of antibodies, facilitates the projection of homotrimers from the viral surface, binds to human ACE2 receptor, and finally mediates membrane fusion and transport (Tortorici & Veesler, 2019).
T52 5555-5715 Sentence denotes Spike (S) protein initially cleaves itself into two functional subunits (S1 and S2) which remain non-covalently bound to each other in a prefusion conformation.
T53 5716-5928 Sentence denotes The S1 subunit is responsible for binding to ACE2, whereas S2 subunit has role in viral and host cell membrane fusion (Belouzard et al., 2009; Bosch et al., 2003; Burkard et al., 2014; Kirchdoerfer et al., 2016).
T54 5929-6111 Sentence denotes SARS-CoV-2 also encodes a non-structural replicase polyprotein that is processed by viral proteases viz. the primary viral proteinase (3CL-pro) and the papain-like protease (PL-pro).
T55 6112-6208 Sentence denotes 3CL-pro (Nsp5) regulates viral replication and cleavage of Nsp4 to Nsp16 (Ziebuhr et al., 2000).
T56 6209-6308 Sentence denotes This main protease is another attractive therapeutic target (Anand et al., 2003; Liu et al., 2020).
T57 6309-6615 Sentence denotes PL-pro, another crucial non-structural protein, is a virally encoded cysteine protease which has a role in N-terminal processing of viral polyproteins causing release of Nsp1, Nsp2 and Nsp3 which are essential for viral replication to proceed in a correct manner (Chen et al., 2020; Harcourt et al., 2004).
T58 6616-6721 Sentence denotes Recently, the structure of two critical non-structural proteins in complex Nsp10/Nsp16 has been reported.
T59 6722-6844 Sentence denotes The complex is responsible for the modification of genetic material of virus in order to camouflage it with host cell DNA.
T60 6845-6949 Sentence denotes This permits viral evasion and escape from the immune cells of the host, thereby perpetuating infection.
T61 6950-7127 Sentence denotes Thus, targeting the Nsp10/Nsp16 complex might help in the effective combat and eradication of COVID-19 infection (https://www.anl.gov/article/new-drug-target-found-for-covid19).
T62 7128-7356 Sentence denotes In the past decade, hundreds of drugs were withdrawn from the market as a result of their failure to either exhibit the desired biological activity or due to their unexpected toxicity and adverse side effects in clinical trials.
T63 7357-7626 Sentence denotes These poor outcomes may be attributed due to lack of a planned and systematic approach to rational drug design and discovery leading to losses that place a heavy burden on the poor economic sections of the society in particular and the third world countries in general.
T64 7627-7803 Sentence denotes In the post genomic era, in silico prediction of chemical leads has a significant role in drug discovery, which has proven to be more time and cost effective (Xu et al., 2012).
T65 7804-7891 Sentence denotes Clinical studies of various drug like properties are very time consuming and expensive.
T66 7892-8034 Sentence denotes Therefore, computational techniques come is as helpful and handy before going for the expensive in vitro, in vivo studies and clinical trials.
T67 8035-8233 Sentence denotes Computational techniques can filter and predict the druglikeness, absorption, distribution, metabolism, excretion, and toxicity (ADMET) criteria of a prospective drug candidate (Cheng et al., 2012).
T68 8234-8458 Sentence denotes In this context, Ayurveda, the Indian traditional system of medicine encompassing a plethora of medicinal plants and their phytoconstituents(s) with proven diverse pharmacological activities, has remained largely unexplored.
T69 8459-8626 Sentence denotes Thus, Ayurveda offers a staggering array of natural products and prospective therapeutic agents for evaluation against the causal agent of the ongoing global pandemic.
T70 8627-9062 Sentence denotes Withania somnifera (WS), commonly known as ‘Indian Ginseng’ and ‘Ashwagandha’ in Hindi, belongs to family Solanaceae (Figure 1) and holds an important position in Ayurveda owing to its broad therapeutic spectrum and a plethora of pharmacological activities including anti-spasmodic, anti-arthritic, anti-inflammatory, sedative, nerve soothing, hypotensive, antioxidant, immunomodulatory, anti-stress and anti-tumor (Jain et al., 2012).
T71 9063-9309 Sentence denotes Figure 1. (a) Withania somnifera (L.) Dunal Habit (b) Leaves (c) Flower (d) Fruit (e) Stem (Image courtesy naturesalive.wordpress.com, www.nmpb.nic.in, www.flowersofindia.net, Jain et al. (2012), https://stock.adobe.com/in/search?k=ashwagandha).
T72 9310-9507 Sentence denotes The plant comprises 29 natural secondary metabolites commonly called as ‘withanolides’ extracted from leaves, stems, roots, and flowers which are known for their potent anti-tumor effect (Table 1).
T73 9508-9765 Sentence denotes Some previous studies have reported the anti-influenza properties of active constituents of WS against H1N1 influenza and antiviral activity of withanone from WS against novel coronavirus (Balakrishnan et al., 2014; Cai et al., 2015; Varshney et al., 2020).
T74 9766-9857 Sentence denotes However, still, not much is known regarding the antiviral activity of WS phytoconstituents.
T75 9858-10060 Sentence denotes Therefore, one of the main aims of the present study was to evaluate the antiviral activity of WS phytoconstituents against major target proteins of SARS-CoV-2, the causal agent of the ongoing pandemic.
T76 10061-10069 Sentence denotes Table 1.
T77 10071-10116 Sentence denotes List of withanolides from Withania somnifera.
T78 10117-10145 Sentence denotes Withaferin A Withanolide A
T79 10146-10158 Sentence denotes PubChem CID:
T80 10159-10179 Sentence denotes 265237 PubChem CID:
T81 10180-10188 Sentence denotes 11294368
T82 10189-10245 Sentence denotes Molecular Formula: C28H38O6 Molecular Formula: C28H38O6
T83 10246-10261 Sentence denotes Chemical Class:
T84 10262-10296 Sentence denotes Steroidal Lactone Chemical Class:
T85 10297-10314 Sentence denotes Steroidal Lactone
T86 10315-10344 Sentence denotes Withanolide B Withanolide D
T87 10345-10357 Sentence denotes PubChem CID:
T88 10358-10380 Sentence denotes 14236711 PubChem CID:
T89 10381-10387 Sentence denotes 161671
T90 10388-10444 Sentence denotes Molecular Formula: C28H38O5 Molecular Formula: C28H38O6
T91 10445-10460 Sentence denotes Chemical Class:
T92 10461-10495 Sentence denotes Steroidal Lactone Chemical Class:
T93 10496-10513 Sentence denotes Steroidal Lactone
T94 10514-10539 Sentence denotes Withanolide E Withanone
T95 10540-10552 Sentence denotes PubChem CID:
T96 10553-10573 Sentence denotes 301751 PubChem CID:
T97 10574-10582 Sentence denotes 21679027
T98 10583-10639 Sentence denotes Molecular Formula: C28H38O7 Molecular Formula: C28H38O6
T99 10640-10655 Sentence denotes Chemical Class:
T100 10656-10690 Sentence denotes Steroidal Lactone Chemical Class:
T101 10691-10708 Sentence denotes Steroidal Lactone
T102 10709-10737 Sentence denotes Viscosalactone B Anaferine
T103 10738-10750 Sentence denotes PubChem CID:
T104 10751-10773 Sentence denotes 57403080 PubChem CID:
T105 10774-10780 Sentence denotes 443143
T106 10781-10838 Sentence denotes Molecular Formula: C28H40O7 Molecular Formula: C13H24N2O
T107 10839-10854 Sentence denotes Chemical Class:
T108 10855-10889 Sentence denotes Steroidal Lactone Chemical Class:
T109 10890-10909 Sentence denotes Piperidine Alkaloid
T110 10910-10911 Sentence denotes  
T111 10912-10927 Sentence denotes Withasomnine  
T112 10928-10940 Sentence denotes PubChem CID:
T113 10941-10950 Sentence denotes 442877  
T114 10951-10981 Sentence denotes Molecular Formula: C12H12N2  
T115 10982-10997 Sentence denotes Chemical Class:
T116 10998-11261 Sentence denotes Pyrazole Alkaloid   Withanolides, including withanolides A, B, D, E, anaferine, withaferin A, withasomnine, withanone and viscosalactone B (Table 1) are responsible for various pharmacological activities as detailed above (Jain et al., 2012; Misra et al., 2008).
T117 11262-11330 Sentence denotes They belong to chemical classes of alkaloids and steroidal lactones.
T118 11331-11464 Sentence denotes Agents that can preferentially bind to ACE2 receptor can be thought of as promising ‘preventive’ agents against SARS-CoV-2 infection.
T119 11465-11690 Sentence denotes Alternately, agents that bind to main viral proteins can interfere and/or block crucial stages in the viral life cycle such as viral entry, replication, membrane fusion and hence, can function as promising therapeutic agents.
T120 11691-11928 Sentence denotes The present paper attempts to highlight the preventive/therapeutic potential of withanolides from WS as promising antiviral agents to augment our limited armamentarium of drugs available against SARS-CoV-2 to effectively combat COVID-19.
T121 11929-12360 Sentence denotes All the standard reference drugs used in the study like losartan, procainamide, cinacalcet, arbidol, hydroxychloroquine, oberadilol and poziotinib are FDA-approved drugs that were chosen for their specific binding to proteins selected for the study viz. human ACE2 receptor, SARS-CoV and SARS-CoV-2 target proteins (Spike S glycoprotein, protease) as referenced in literature (Arya et al., 2020; Liu et al., 2020, Wu et al., 2020).
T122 12361-12504 Sentence denotes Since there is no available literature on Nsp10/Nsp16 complex, two randomly selected reference drugs were chosen against it in binding studies.