LitCovid-sentences  

PMC:7755033 / 104011-111037 JSONTXT 2 Projects

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Id Subject Object Predicate Lexical cue
T1068 0-2 Sentence denotes 4.
T1069 4-14 Sentence denotes Discussion
T1070 15-187 Sentence denotes The current outbreak of SARS-CoV-2, a life threatening zoonotic coronavirus has made us painfully realize that existing and available options for its treatment are limited.
T1071 188-379 Sentence denotes Although, several efforts were made to treat SARS in 2002 and MERS in 2013, none of the past or existing efforts to treat the ongoing pandemic of 2020 has been found to be fruitful till date.
T1072 380-493 Sentence denotes Existing therapeutic options include the use of repurposed/repositioned drugs for treatment of COVID-19 pandemic.
T1073 494-649 Sentence denotes Development of effective vaccine candidates is also underway but would take considerable time and effort to produce fruitful results as shown in Figure 13.
T1074 650-844 Sentence denotes Prospective therapeutic discovery against coronavirus can be subdivided into two groups depending on the target: one acting upon the virus and the other acting on the human innate immune system.
T1075 845-999 Sentence denotes The latter plays a significant role in controlling the viral replication and secretion of cytokines are expected to improve the immune system functioning.
T1076 1000-1010 Sentence denotes Figure 13.
T1077 1012-1053 Sentence denotes Stages in drug discovery and development.
T1078 1054-1137 Sentence denotes In our every tryst with nature, we always perceive and find more than what we seek.
T1079 1138-1216 Sentence denotes Ancient Vedic literature has described nature as the ‘mother of all healings’.
T1080 1217-1333 Sentence denotes Nature is known to have its own antidote against all natural and mankind activity induced maladies such as COVID-19.
T1081 1334-1512 Sentence denotes The benefits of ‘Ecotherapy’ and ‘healing power’ of nature have led to the discovery of several miraculous systems of healing amongst which Ayurveda holds a significant position.
T1082 1513-1682 Sentence denotes Withanolides are a group of at least 300 naturally occurring steroids built on an ergostane skeleton that are produced as secondary metabolites in several plant species.
T1083 1683-1784 Sentence denotes They are composed specifically of triterpenoids bearing around 28-carbon backbone (Cai et al., 2015).
T1084 1785-1959 Sentence denotes Given the importance of WS in Ayurveda as well as ethnopharmacology, majority of the studies reported in literature are confined to its antitumor and rejuvenating properties.
T1085 1960-2037 Sentence denotes There is scanty information available regarding the antiviral activity of WS.
T1086 2038-2207 Sentence denotes In the present paper, an attempt has been made to explore the antiviral potential of WS against COVID-19 using molecular and chemoinformatic tools and in silico methods.
T1087 2208-2360 Sentence denotes Generally, an orally active drug candidate cannot have more than one violation of Lipinski’s criteria otherwise it might compromise its bioavailability.
T1088 2361-2463 Sentence denotes Good drug candidates with MW < 500 can be administered easily and are readily diffusible and absorbed.
T1089 2464-2592 Sentence denotes For optimal biological activity, the number of rotatable bonds should be <10, indicating a higher amount of molecular stability.
T1090 2593-2765 Sentence denotes Similarly, total polar surface area (TPSA) should coincide with hydrogen bonding of a molecule and characterize the delivery properties of the drug which should be <160 Å2.
T1091 2766-2883 Sentence denotes For a high oral bioavailability, the absorption rate determined from TPSA should be >50% (Balakrishnan et al., 2014).
T1092 2884-3078 Sentence denotes Interestingly, none of the phytocomponents of WS exhibited Lipinski’s violation, however, the standard drugs cinacalcet and poziotinib displayed 1 violation of Lipinski’s rule of five (Table 2).
T1093 3079-3235 Sentence denotes In addition, the selected phytoconstituents exhibited no violations of Veber, Egan and Muegge filters thereby indicating their druglike character (Table 3).
T1094 3236-3487 Sentence denotes Prior to selection of WS phytoconstituents, their ADMET properties were calculated using online database (admetSAR), which provides latest and most inclusive manually created data for various chemicals with known ADMET properties (Cheng et al., 2012).
T1095 3488-3671 Sentence denotes Interestingly, in the present study, most of the WS phytoconstituents exhibited positive results of ADME and none of the phytoconstituents were predicted to have any mutagenic effect.
T1096 3672-3798 Sentence denotes Further, in case of Caco-2 permeability, anaferine and withasomnine exhibited positive results indicating Caco-2 permeability.
T1097 3799-4084 Sentence denotes Positive results for Caco-2 indicate good permeability characteristics of compounds under evaluation since Caco-2 cells express a number of transporter and efflux proteins as well as Phase II conjugation enzymes for metabolic transformation of test substances (van Breemen & Li, 2005).
T1098 4085-4290 Sentence denotes Ames test is a short-term bacterial reverse mutation assay used for evaluating compounds for their ability to induce genetic damage and frame shift mutations (Ames et al., 1975; Mortelmans & Zeiger, 2000).
T1099 4291-4369 Sentence denotes Mutagenic effects bear a close connection to carcinogenesis (Xu et al., 2012).
T1100 4370-4491 Sentence denotes Interestingly, in the present study, none of the chosen WS phytoconstituents were predicted to have any mutagenic effect.
T1101 4492-4698 Sentence denotes The 3CL-pro of CoVs is necessary for the proteolytic maturation of the virus and a potential drug target to prevent infection from spreading by inhibiting the cleavage of viral proteins (Tian et al., 2015).
T1102 4699-4864 Sentence denotes Therefore, inhibition of such proteases which have a role in virus replication are often used as treatment strategies in antiviral drug therapeutics (Delaney, 2004).
T1103 4865-5005 Sentence denotes Human ACE2 expression in the airway epithelia appears to be critical as an entry receptor for SARS-CoV and SARS-CoV-2 (Morris et al., 1998).
T1104 5006-5222 Sentence denotes The transmembrane spike (S) glycoprotein present on the surface of coronaviruses facilitates their entry into the cell via ACE2 and is considered to be another prime target for antiviral agents against coronaviruses.
T1105 5223-5363 Sentence denotes These findings have implications for understanding disease pathogenesis and opportunity to identify potential drug candidates for treatment.
T1106 5364-5497 Sentence denotes Nelfinavir and lopinavir are viral protease inhibitors used against HIV infection but are reported to possess high cytotoxic effects.
T1107 5498-5693 Sentence denotes Lopinavir and ritonavir are viral protease inhibitors recommended for the treatment of SARS and MERS having similar mechanisms of action as nelfinavir and lopinavir. (Miyamoto and Kollman, 1992).
T1108 5694-5864 Sentence denotes To elucidate the binding affinity, docking studies of various withanolides found in WS were carried out on human ACE2 receptor, SARS-CoV and SARS-CoV-2 specific proteins.
T1109 5865-6001 Sentence denotes Among various phytoconstituents, withanolide A displayed strong binding affinity to SARS-CoV spike glycoprotein (BE: −9.78 kcal/mol, Kd:
T1110 6002-6067 Sentence denotes 67.23 nM), SARS-CoV-2 spike glycoprotein (BE: −7.18 kcal/mol, Kd:
T1111 6068-6132 Sentence denotes 5.48 µM), SARS-CoV 3CL-pro main protease (BE:-8.93 kcal/mol, Kd:
T1112 6133-6205 Sentence denotes 285.01 nM) and SARS-CoV-2 Nsp10/Nsp-16 complex (BE: −10.38 kcal/mol, Kd:
T1113 6206-6216 Sentence denotes 24.67 nM).
T1114 6217-6342 Sentence denotes On the basis of binding energy, withanolides A and B and withanone were found to be the most effective phytocomponents in WS.
T1115 6343-6676 Sentence denotes The present study reports for the first time the antiviral efficacy of medicinal herbs like Withania somnifera that form the crux of Ayurveda, the Indian traditional system of medicine as a viable alternative to chemosynthetic drugs for preventing/blocking entry of SARS-CoV-2 into host cells and also inhibiting viral main protease.
T1116 6677-6913 Sentence denotes In conclusion, the most effective withanolides viz. withanolide A, withanolide B and withanone can be exploited and studied in future both in vitro and in vivo as prospective first choice antiviral agents for curbing COVID-19 infection.
T1117 6914-7026 Sentence denotes This preliminary study provides validation for plausible inhibitory potential of major withanolides found in WS.