1. Introduction The novel coronavirus disease 2019 (COVID-19) has become a major threat worldwide due to its fast-spreading nature. This disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The entry of this coronavirus to the host cell is mediated through the transmembrane spike glycoproteins (Hasan et al., 2020). This glycoprotein consists of two subunits and is reported to have a similar affinity to the human angiotensin-converting enzyme 2 (ACE2) as that of the severe acute respiratory syndrome coronavirus (SARS-CoV), which in turn results in efficient spreading of SARS-CoV-2 in humans (Walls et al., 2020). The spike glycol protein binds to its receptor human ACE2 by its receptor-binding domain (RBD) and is activated proteolytically by human protease (Shang et al., 2020). The interaction of the RBD of the spike glycoprotein to ACE2 is carried out by ARG403, TYR453, SER494, TYR495, PHE497, GLN498, THR500, ASN501, TYR505 residues of spike glycoprotein (Lan et al., 2020). The interaction of RBD Spro to ACE2 can be inhibited by the small molecules that interact with the above residues of RBD spike protein (Spro). On the other hand, the SARS-CoV-2 main protease (Mpro), also known as chymotrypsin-like protease, or 3-C-like protease (3CLpro), plays a vital role in processing the polyproteins through the translation of viral RNA. This protease is reported to have a minimum of 11 cleavage sites resulting in viral replication and toxicity (Zhang et al., 2020). The inhibition of these two viral targets can actively block the fusion and replication of SARS-CoV-2. Currently, researchers are working globally for finding treatment for this disease in identifying a specific drug or vaccine that can inhibit viral replication at the earliest possible. The devastation of this disease is vividly seen from the data on the WHO website, which shows the infected patient number more than 245 lakhs and casualties more than 8 lakhs, worldwide from 216 countries, and still, it is continuing (https://www.who.int/emergencies/diseases/novel-coronavirus-2019, 29 August 2020). Currently, there are no approved drugs and vaccines for the treatment of COVID-19, but a few drugs such as remdesivir, hydroxychloroquine, etc. are under restricted use in case of emergency (Magagnoli et al., 2020). Meanwhile, the computational tools, molecular docking and molecular dynamics (MD) have gained attention as essential tools to investigate potential inhibitor molecules (Anurag et al., 2020; Gupta et al., 2020; Sourav et al., 2020). Choy et al. reported in-vitro studies showing remdesivir, lopinavir, emetine and homoharringtonine inhibits SARS-CoV-2 replication (Choy et al., 2020). Similarly, Wang et al. reported the inhibition property of remdesivir and chloroquine against novel coronavirus (Wang et al., 2020). In addition to different drug compounds, researchers also searched for natural molecules having antiviral activity. Natural constituents from foods, spices, herbs are also being found to have anti-infective properties. In this context, small active molecules present in natural products and their derivatives have gained tremendous attention as a source of therapeutic agents due to structural diversity for many years. From 1940 to 2014, the US Food and Drug Administration (FDA) has approved about 49% of all small molecules that are natural products or derivates linked directly to those molecules (Newman & Cragg, 2016). The compound of essential garlic oil, a spice used in food, is reported as an inhibitor using the molecular docking method (Thuy et al., 2020). There are several recent studies on the inhibition of SARS-CoV-2 using many different natural and antiviral molecules (Al-Khafaji et al., 2020; Joshi et al., 2020; D. Kumar, Kumari, et al., 2020; Muralidharan et al., 2020). Recently, Das et al., using blind molecular docking, investigated for the potential inhibitors of SARS-CoV-2 Mpro (Sourav et al., 2020). Molecules studied by Das et al. are drug molecules, antivirals, antifungals, anti-nematodals and anti-protozoals in addition to natural compounds. Besides, natural molecules such as alkaloids and terpenoids from African medicinal plants were studied by Gyebi et al. for the inhibition property against SARS-CoV-2 Mpro (Gyebi et al., 2020). Recently, Umesh et al. screened compounds from Indian spices as potent inhibitors of SARS-CoV-2 Mpro (Umesh et al., 2020). Every spice has a particular aroma, colour and flavour due to the presence of specific molecules in them, and also, have antiviral properties (Aboubakr et al., 2016; Astani et al., 2010; Brochot et al., 2017; Chang et al., 2013; Choi, 2016; Mair et al., 2016; Zhang et al., 2014). These properties of the spice molecules compel us to conduct the present study, where we investigated the inhibition property of molecules present in various spices against the SARS-CoV-2 RBD Spro and SARS-Cov-2 Mpro using molecular docking and MD simulation studies. The compounds tested and their source of origin with PubChem ID are listed in Supplementary Table S1. Table 1. Predicted data of docking score, solubility, pharmacokinetics, drug-likeness and medicinal chemistry of the screened spice molecules. Sl. No. Molecule Binding energy (kcal/mol) ESOL Log S Ali Log S Silicos-IT LogSw GI absorption BBB permeant Pgp substrate Log Kp (cm/s) Bioavailability score Synthetic accessibility Mpro RBD Spro 1 2-Decenoic acid –5.4 –4.6 –2.8 –4.23 –2.15 High Yes No –4.68 0.56 2.44 2 α-Terpinyl acetate –5.5 –5.0 –3.35 –4.21 –2.36 High Yes No –4.69 0.55 3.13 3 Capsaicin –6.4 –5.5 –3.53 –4.5 –4.87 High Yes No –5.62 0.55 2.32 4 Carvone –6.2 –5.2 –2.41 –2.72 –2.16 High Yes No –5.29 0.55 3.33 5 Cinnamaldehyde –5.7 –5.1 –2.17 –1.88 –2.4 High Yes No –5.76 0.55 1.65 6 Cuminaldehyde –5.9 –5.1 –2.52 –2.37 –3.15 High Yes No –5.52 0.55 1.0 7 Dipropyl disulfide –3.1 –3.0 –2.14 –3.42 –2.48 High Yes No –5.3 0.55 2.79 8 Eucalyptol –5.2 –4.9 –2.52 –2.59 –2.45 High Yes No –5.3 0.55 3.65 9 Linalool –5.5 –4.9 –2.4 –3.06 –1.84 High Yes No –5.13 0.55 2.74 10 Vanillin –5.7 –4.8 –1.82 –1.78 –1.88 High Yes No –6.37 0.55 1.15 11 Thymol –5.8 –5.3 –3.19 –3.4 –3.01 High Yes No –4.87 0.55 1.0 12 Sabinene hydrate –5.2 –4.7 –2.07 –2.18 –1.91 High Yes No –5.74 0.55 2.82 13 Piperine –7.3 –6.4 –3.74 –3.96 –3.0 High Yes No –5.58 0.55 2.92 14 Menthol –5.6 –5.2 –2.88 –3.5 –1.48 High Yes No –4.84 0.55 2.63 15 Eugenol –6.0 –5.0 –2.46 –2.53 –2.79 High Yes No –5.69 0.55 1.58 16 Estragole –5.7 –4.8 –3.09 –3.24 –3.35 High Yes No –4.81 0.55 1.28 17 Gingerol –6.1 –5.5 –2.96 –3.82 –4.58 High Yes No –6.14 0.55 2.81 18 Shogaol –5.8 –5.4 –3.7 –4.67 –4.8 High Yes No –5.15 0.55 2.51 19 Paradol –6.0 –4.6 –3.72 –4.79 –5.52 High Yes No –5.08 0.55 2.28 20 Zingerone –6.0 –5.1 –1.8 –1.68 –3.1 High Yes No –6.7 0.55 1.52 21 Borneol –5.7 –4.3 –2.51 –2.8 –1.91 High Yes No –5.31 0.55 3.43 22 Bornyl acetate –5.3 –4.8 –3.63 –4.57 –2.58 High Yes No –4.44 0.55 3.64 23 Citral –5.5 –4.7 –2.43 –3.05 –1.96 High Yes No –5.08 0.55 2.49 24 Citronellal –4.8 –4.8 –2.88 –3.88 –2.33 High Yes No –4.52 0.55 2.57 25 2-Undecanone –4.9 –4.3 –2.94 –4.15 –3.83 High Yes No –4.43 0.55 1.72 26 Geranyl acetate –5.4 –4.8 –3.21 –4.3 –2.52 High Yes No –4.63 0.55 2.72 27 Nerolidol –5.8 –5.0 –3.8 –4.99 –3.15 High Yes No –4.23 0.55 3.53 28 Terpinen-4-ol –5.2 –5.5 –2.78 –3.36 –1.91 High Yes No –4.93 0.55 3.28 29 Terpineol –5.7 –5.2 –2.87 –3.49 –1.69 High Yes No –4.83 0.55 3.24 30 Decanal –4.7 –3.9 –2.67 –3.85 –3.44 High Yes No –4.56 0.55 1.62