The spike protein of coronavirus is key target for drug development and other pharmacological interventions. In current study, we performed an integrative approach to predict antigenic sites in SARS-CoV-2 spike receptor binding domain and found nine potential antigenic sites. The predicted antigenic sites were then assessed for possible molecular similarity with other known antigens in different organisms. Out of nine sites, seven sites showed molecular similarity with 54 antigenic determinants found in twelve pathogenic bacterial species (Mycobacterium tuberculosis, Mycobacterium leprae, Bacillus anthracis, Borrelia burgdorferi, Clostridium perfringens, Clostridium tetani, Helicobacter Pylori, Listeria monocytogenes, Staphylococcus aureus, Streptococcus pyogenes, Vibrio cholera and Yersinia pestis), two malarial parasites (Plasmodium falciparum and Plasmodium knowlesi) and influenza virus A. Most of the bacterial antigens that displayed molecular similarity with antigenic sites in SARS-CoV-2 RBD (receptor binding domain) were toxins and virulent factors. Antigens from Mycobacterium that showed similarity were mainly involved in modulating host cell immune response and ensuring persistence and survival of pathogen in host cells. Presence of a large number of antigenic determinants, similar to those in highly pathogenic microorganisms, not merely accounts for complex etiology of the disease but also provides an explanation for observed pathophysiological complications, such as deregulated immune response, unleashed or dysregulated cytokine secretion (cytokine storm), multiple organ failure etc., that are more evident in aged and immune-compromised patients. Over-representation of antigenic determinants from Plasmodium and Mycobacterium in all antigenic sites suggests that anti-malarial and anti-TB drugs can prove to be clinical beneficial for COVID-19 treatment. Besides this, anti-leprosy, anti-lyme, anti-plague, anti-anthrax drugs/vaccine etc. are also expected to be beneficial in COVID-19 treatment. Moreover, individuals previously immunized/vaccinated or had previous history of malaria, tuberculosis or other disease caused by fifteen microorganisms are expected to display a considerable degree of resistance against SARS-CoV-2 infection. Out of the seven antigenic sites predicted in SARS-CoV-2, a part of two antigenic sites were also predicted as potent T-cell epitopes (KVGGNYNYL^444-452 and SVLYNSASF^366-374) against MHC class I and three (KRISNCVADYSVLYN^356-370, DLCFTNVYADSFVI^389-402, and YRVVVLSFELLHA^508-520) against MHC class II. All epitopes possessed significantly lower predicted IC50 value which is a prerequisite for a preferred vaccine candidate for COVID-19.

冠状病毒的刺突蛋白是药物开发和其他药理干预的关键目标。在当前的研究中，我们采用了一种综合方法来预测 SARS-CoV-2 刺突受体结合域中的抗原位点，并发现了九个潜在的抗原位点。然后评估预测的抗原位点与不同生物体中其他已知抗原的可能分子相似性。在九个位点中，七个位点与 12 种致病菌（结核分枝杆菌、麻风分枝杆菌、炭疽杆菌、伯氏疏螺旋体、产气荚膜梭菌、破伤风梭菌、幽门螺杆菌、单核细胞增生李斯特菌、金黄色葡萄球菌、化脓性链球菌）中发现的 54 个抗原决定簇具有分子相似性, 霍乱弧菌和鼠疫耶尔森氏菌）、两种疟疾寄生虫（恶性疟原虫和诺氏疟原虫）和甲型流感病毒。大多数与 SARS-CoV-2 RBD（受体结合域）抗原位点分子相似的细菌抗原是毒素和毒力因子。分枝杆菌抗原显示相似性的主要参与调节宿主细胞免疫反应和确保病原体在宿主细胞中的持久性和存活。大量抗原决定簇的存在，类似于高致病性微生物中的抗原决定簇，不仅解释了该疾病的复杂病因，而且还解释了观察到的病理生理并发症，例如免疫反应失调、细胞因子分泌释放或失调（细胞因子风暴)、多器官功能衰竭等，在老年和免疫功能低下的患者中更为明显。来自疟原虫和分枝杆菌的抗原决定簇的过度表达在所有抗原位点的研究表明，抗疟疾和抗结核药物可以证明对 COVID-19 治疗有临床益处。除此之外，抗麻风病、抗莱姆病、抗鼠疫、抗炭疽药物/疫苗等也有望对COVID-19治疗有益。此外，预计先前免疫/接种疫苗或有疟疾、肺结核或其他由 15 种微生物引起的疾病病史的个体将对 SARS-CoV-2 感染表现出相当程度的抵抗力。在 SARS-CoV-2 中预测的七个抗原位点中，两个抗原位点的一部分也被预测为针对 MHC I 类和三类MHC ^{（KRINSCVADYSVLYN 356-第370}章、^389-402和 YRVVVLSFELLHA ^508-520 ) 针对 MHC II 类。所有表位都具有显着较低的预测 IC50 值，这是 COVID-19 首选候选疫苗的先决条件。