Targeting the initiation and termination codons of SARS-CoV-2 spike protein as possible therapy against COVID-19: the role of novel harpagide 5-O-β-D-glucopyranoside from Clerodendrum volubile P Beauv. (Labiatae)

Abstract

The global spread of the coronavirus infections disease − 2019 (COVID-19) and the search for new drugs from natural products particularly from plants are receiving much attention recently. In this study, the therapeutic potential of a new iridoid glycoside isolated from the leaves of Clerodendrum volubile against COVID-19 was investigated. Harpagide 5-O-β-D-glucopyranoside (HG) was isolated, characterised and investigated for its druglikeness, optimized geometry, and pharmacokinetics properties. Its immunomodulatory was determined by chemiluminescence assay using polymorphonuclear neutrophils (PMNs) in addition to T-cell proliferation assay. In silico analysis was used in determining its molecular interaction with severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). HG displayed potent druglikeness properties, with no inhibitory effect on cytochrome P 450 (1A2, 2C19, 2C9, 2D6 and 3A4) and a predicted LD 50 of 2000 mg/kg. Its 1 H-NMR chemical shifts showed a little deviation of 0.01 and 0.11 ppm for H-4 and H-9, respectively. HG significantly suppressed oxidative bursts in PMNs, while concomitantly inhibiting T-cell proliferation. It also displayed a very strong binding affinity with the translation initiation and termination sequence sites of spike (S) protein mRNA of SARS-COV-2, its gene product, and host ACE2 receptor. These results suggest the immunomodulatory properties and anti-SARS-COV-2 potentials of HG which can be explored in the treatment and management of COVID-19. Communicated by Ramaswamy H. Sarma

Translational suppression of SARS-COV-2 ORF8 protein mRNA as a Viable therapeutic target against COVID-19: Computational studies on potential roles of isolated compounds from Clerodendrum volubile leaves

“…Cytokine storms have been implicated in the pathophysiology of COVID-19 infection and its complications. This is depicted by exacerbated cellular levels of proinflammatory cytokines such as TNF-α, IL-2 and IL-7 [ [6] , [7] , [8] ]. ORF8 has been reported to play a major role in SARS-CoV-2 induction of cytokine storms in COVID-19 [ 16 , 18 , 19 ].…”

“…SARS-CoV-2 has been reported to cause infection by triggering an excessive immune response depicted by aggravated levels of macrophage inflammatory protein 1-α, tumour necrosis factor-α (TNF-α), interleukins (IL)-2 and −7, monocyte chemoattractant protein 1, and granulocyte colony stimulating factor [ [6] , [7] , [8] ]. This process is regarded as cytokine storm and has been implicated in the pathology and severity of COVID-19 and its mortality [ 9 , 10 ].…”

“…The leaves have also been linked to improved antioxidant activities in type 2 diabetes and cancers [ [23] , [24] , [25] , [26] ]. Its immunomodulatory properties have been linked to the ability of the leaves and flowers, as well as protocatechuic acid, pectolinarigenin, and harpagide 5-O-β- d -glucopyranoside (isolated from the leaves), to suppress the oxidative burst in isolated neutrophils and macrophages [ 6 , 23 , 27 , 28 ]. A new compound, harpagide 5-O-β- d -glucopyranoside isolated from C. volubile leaves, was proposed via in silico studies as a suitable inhibitor of initiation and termination codons of SARS-CoV-2 spike protein [ 6 ].…”

Traditional Uses, Nutritional and Pharmacological Potentials of Clerodendrum volubile

“…In addition, the use of supplements that can boost the host immune system has been documented as a good strategy to fight the virus [ 85 ]. Unfortunately, research on the exploration of medicinal plants for the development of antiviral drugs against coronavirus is slow, as much attention has been currently geared towards vaccine development globally [ 86 , 87 ]. Erukainure and colleagues [ 86 ] have investigated the inhibitory potential of harpagide 5- O -β-D-glucopyranoside, a new iridoid glycoside isolated from methanolic leaves of C. volubile against SARS CoV-2.…”

Targeting of Protein’s Messenger RNA for Viral Replication, Assembly and Release in SARS-CoV-2 Using Whole Genomic Data From South Africa: Therapeutic Potentials of Cannabis Sativa L

“…Several studies have reported the potentials of medicinal plants in the treatment and management of COVID-19 and its complications (Benarba and Pandiella, 2020;Erukainure et al, 2020;Vellingiri et al, 2020). These therapeutic properties have been attributed to the phytochemical constituents of the plants.…”