Alkaloids as Potential Phytochemicals against SARS-CoV-2: Approaches to the Associated Pivotal Mechanisms

Abstract

Since its inception, the coronavirus disease 2019 (COVID-19) pandemic has infected millions of people around the world. Therefore, it is necessary to find effective treatments against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), as it is the viral source of COVID-19. Alkaloids are one of the most widespread plant-derived natural compounds with prominent antiviral effects. Accordingly, these phytochemicals have been promising candidates towards discovering effective treatments for COVID-19. Alkaloids have shown potential anti-SARS-CoV activities via inhibiting pathogenesis-associated targets of the Coronaviridae family that are required for the virus life cycle. In the current study, the chemistry, plant sources, and antiviral effects of alkaloids, as well as their anti-SARS-CoV-2 effect with related mechanisms, are reviewed towards discovering an effective treatment against COVID-19.

Potential of Quinine Sulfate for COVID-19 Treatment and Its Safety Profile: Review

“… 45 , 46 As fever is one of the most common side effects of COVID-19 and quinine has prominent antipyretic effects, these alkaloids could be introduced as a treatment for handling this complication of COVID-19. 35 , 47 …”

“…Both will block viral mRNA translation through PKR activation and degrade poly mRNA by activating RNAse(L), thereby inhibiting protein synthesis. [ 51 ] 8 Antiviral activity via DNA intercalation [ 46 ] 9 -Antipyretic activity -Antiviral activity against SARS-CoV-2 with EC 50 10.7 μM, EC 90 38.8 μM -Low toxicity (CC 50 > 100 μM) in Vero E6 cells -Interacts with Mpro (−6.2 kcal/mol) and S protein (−5.7 kcal/mol) [ 47 ] Abbreviation : HSV-1, Herpes simplex virus-1; IAV, Influenza A virus; TNFα, Tumor Necrosis Factor-α; IL, interleukin; INFγ, Interferon γ; CCL2, C-C Motif Chemokine Ligand 2; CXCL10, C-X-C motif Chemokine Ligand 10; ACE-2, Angiotensin Converting Enzyme-2; RIG-I, Retinoic acid-Inducible Gene I; EC, Effective Concentration. …”

Genus Sophora: a comprehensive review on secondary chemical metabolites and their biological aspects from past achievements to future perspectives

“…A quinolizidine alkaloid with an unusual endocyclic ring system, aloperine ( 284 ) was extracted from the seeds and leaves of S. alopecuroides L . (Majnooni et al 2021 ). Compound 284 has been identified as a potent hepatitis virus C inhibitor with EC 50 -value of 4.23 ± 0.99 μM (Dang et al 2016 ; Ti et al 2021 ).…”

“…A rare 1,4-diazaindan-type alkaloid; flavascensine ( 279 ) was also isolated from S. flavescens roots (Wang et al 2019a ; Ti et al 2021 ). Sophaline E ( 282 ), the first example of sparteine-indolizine alkaloid, sophaline G ( 283a ) and sophaline H ( 283b ), the epimeric normatrine-julolidine alkaloids with unusual skeletons were isolated from S. alopecuroides and have showed antiviral activities against HBV (Wang et al 2019a ; Li et al 2020d ; Majnooni et al 2021 ). A quinolizidine alkaloid with an unusual endocyclic ring system, aloperine ( 284 ) was extracted from the seeds and leaves of S. alopecuroides L .…”

“…Coronavirus disease 2019 (COVID-19) is an illness caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Zhang et al 2020a , b , c ; Majnooni et al 2021 ). The ongoing COVID-19 pandemic has created an alarming situation due to its high morbidity and mortality rates, economic losses, and the threat to global health security.…”