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The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has led to over 910,000 deaths worldwide and unprecedented decimation of the global economy. Despite its tremendous impact, the origin of SARS-CoV-2 has remained mysterious and controversial. The natural origin theory, although widely accepted, lacks substantial support. The alternative theory that the virus may have come from a research laboratory is, however, strictly censored on peer-reviewed scientific journals. Nonetheless, SARS-CoV-2 shows biological characteristics that are inconsistent with a naturally occurring, zoonotic virus. In this report, we describe the genomic, structural, medical, and literature evidence, which, when considered together, strongly contradicts the natural origin theory. The evidence shows that SARS-CoV-2 should be a laboratory product created by using bat coronaviruses ZC45 and/or ZXC21 as a template and/or backbone. Building upon the evidence, we further postulate a synthetic route for SARS-CoV-2, demonstrating that the laboratory-creation of this coronavirus is convenient and can be accomplished in approximately six months. Our work emphasizes the need for an independent investigation into the relevant research laboratories. It also argues for a critical look into certain recently published data, which, albeit problematic, was used to support and claim a natural origin of SARS-CoV-2. From a public health perspective, these actions are necessary as knowledge of the origin of SARS-CoV-2 and of how the virus entered the human population are of pivotal importance in the fundamental control of the COVID-19 pandemic as well as in preventing similar, future pandemics.

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