Virtual Screening of Curcumin and Its Analogs Against the Spike Surface Glycoprotein of SARS-CoV-2 and SARS-CoV

Abstract

COVID-19, a new pandemic caused by SARS-CoV-2, was first identified in 2019 in Wuhan, China. The novel corona virus SARS-CoV-2 and the 2002 SARS-CoV have 74 % identity and use similar mechanisms to gain entry into the cell. Both the viruses enter the host cell by binding of the viral spike glycoprotein to the host receptor, angiotensin converting enzyme 2 (ACE2). Targeting entry of the virus has a better advantage than inhibiting the later stages of the viral life cycle. The crystal structure of the SARS-CoV (6CRV: full length S protein) and SARS-CoV-2 Spike proteins (6M0J: Receptor binding domain, RBD) was used to determine potential small molecule inhibitors. Curcumin, a naturally occurring phytochemical in Curcuma longa, is known to have broad pharmacological properties. In the present study, curcumin and its derivatives were docked, using Autodock 4.2, onto the 6CRV and 6M0J to study their capability to act as inhibitors of the spike protein and thereby, viral entry. The curcumin and its derivatives displayed binding energies, ΔG, ranging from -10.98 to -5.12 kcal/mol (6CRV) and -10.01 to -5.33 kcal/mol (6M0J). The least binding energy was seen in bis-demethoxycurcumin with: ΔG = -10.98 kcal/mol (6CRV) and -10.01 kcal/mol (6M0J). A good binding energy, drug likeness and efficient pharmacokinetic parameters suggest the potential of curcumin and few of its derivatives as SARS-CoV-2 spike protein inhibitors. However, further research is necessary to investigate the ability of these compounds as viral entry inhibitors.<br>

Can Non-steroidal Anti-inflammatory Drugs Affect the Interaction Between Receptor Binding Domain of SARS-COV-2 Spike and the Human ACE2 Receptor? A Computational Biophysical Study

“…This is reflected by the fact that these three compounds were favorably sampled at the interface after the reclassified run in each case as the most thermodynamically feasible, but under the sampling conditions of this study (see Table 1 and Figure 1). Although this is the first study that considers the docking of this type of compound at the level of the RBD-ACE2 interface, our results coincide with those obtained by other authors who have found that Ibuprofen can have a docking score considerably better than other NSAIDs compared to proteins associated with SARS-CoV-2 [44], and that some derivatives could effectively interact with protein regions involved in this complex [76]. These NSAIDs drugs exhibited very close Ki.…”

Targeting Multiple Signal Transduction Pathways of SARS-CoV-2: Approaches to COVID-19 Therapeutic Candidates

“…From another point of view, curcumin reduced the pro-inflammatory cytokines and virus-induced cytokine storm, as well as alleviating lung injury, thereby indicating potential effects in the treatment of COVID-19 [ 237 , 241 ]. According to computational methods, curcumin offers the ability to inhibit the spike protein of SARS-CoV-2 and disrupts viral entry [ 242 ]. Another in silico approach also revealed that curcumin and catechin were used as potential antiviral polyphenols through the dual inhibition of host cell receptors to the virus (mediated by ACE2) and viral protein entry (S-protein).…”

Compounds of plants with activity against SARS-CoV-2 targets

“…Based on their antiviral and anti-inflammatory effects, some phytochemicals such isoflavones, curcumin and diallyl disulfide, have attracted particular attention to providing novel agents in combating coronaviruses and related complications [ 9 ]. These compounds exert antiviral activities against broad spectrum of viruses including adenovirus, Zika virus, herpes simplex virus type 2 (HSV-2), human papiloma virus (HPV), influenza virus, hepatitis virus, and human immunodeficiency virus (HIV), besides MERS-CoV and SARS-CoV [ 10–12 ]. The Brazilian Ministry of Health, 12 herbal medicines derived from plants that are part of the National List of Medicinal Plants of Interest to the Unified Health System (RENISUS), are available for free in the public health network [ 13 ].…”