Global health concerns are increasingly focused on the emergence of controversial pandemics caused by the viruses of the coronaviridae family, leading to severe acute respiratory syndrome. The lack of effective antiviral treatments in the market has intensified these concerns [1], [2], [3]. The recent pandemic of SARS-CoV-2 has highlighted the need for extensive collaboration among various technical and scientific sectors to develop improved solutions and share information [4]. The urgency for antiviral drugs and vaccines is evident, given the millions of illnesses, thousands of fatalities, and ongoing increase in cases. In the absence of specific drug therapies, the temporary solution lies in testing broad-spectrum antivirals capable of targeting multiple diseases [5].

In the fields of agrochemical sciences and medicinal chemistry, α-aminophosphonates have gained significant interest due to their bioisosteric nature, resembling amino acids [6]. The tetrahedral structure of the phosphorus atom allows for substitution with a carbon atom, resulting in transition states comparable to those of receptors bound by amino acids [7]. In recent years, there has been extensive research on α-aminophosphonates owing to their diverse range of biological activities [8], [9].

Aminophosphonates are amino acid analogs in which phosphonic acid or similar groups take the place of a carboxylic moiety. They function as antagonists of amino acids, inhibiting the enzymes responsible for the metabolism of amino acids and influencing the physiological activity of the cell [6], [7], [8], [9]. Also, they exhibit many biological properties such as antiviral [10], [11], antibacterial [12], antifungal [13], anticancer [14], [15], [16], antioxidant [17], and inflammatory [17]. According to the previous overview, some pharmaceutical companies used a-aminophosphonates as an effective antiviral herbicide drugs such as Dufulin [18] and Glyphosate (Round Up®)[19], also as HIV-1 RT inhibitor according to advance care planning (ACP) [20] (Fig. 1).

Additionally, the heterocyclic pyrimidinone moiety is regarded as one of the most widely used components of several medications, including antiviral medications like Acyclovir (treatment of herpes), Idoxuridine (treatment of viral eye infections) [21] and Cidovovir (treatment of cytomegalovirus) [22], (Fig. 1). Also, pyrimidinones have received an abundance of focus because they display a plethora of fascinating biological activity as antiviral [23], anti-inflammatory [24], antitumor [25], [26], [27], antimicrobial [28], and antioxidant activities [27], [29].

Drawing from our expertise in creating bioactive α-aminophosphonates that function as anti-inflammatory, anti-cancer, and antioxidant substances [15], [16], [17], [30], [31], we planned to create novel chemical compositions based on pyrimidinone bioactive skeleton, Fig. 1 that could be investigated as antiviral impact against human Influenza (H1N1) and Coronavirus 229E virus in-silico and in-vitro.