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Abstract Glass fiber reinforced polymer (GFRP) bars are composite materials that, in the field of civil engineering, serve as an alternative for the internal steel reinforcement of concrete structures. The study and development of these material systems in construction are relatively new, requiring targeted research and development to achieve greater adoption. In this scenario, research and standardization play crucial roles. The development and publication of new test methods, material specifications, and other standards, as well as the improvement of the existing ones, allow for quality control, validation, and acceptance. One of these improvements is the evaluation of precision statements of the different ASTM standards related to the physical-mechanical and durability characterization of GFRP bars used as internal concrete reinforcement. Precision refers to how closely test results obtained under specific conditions agree with each other. A precision statement allows potential users to assess the test method’s general suitability for their intended applications. It should provide guidance on the type of variation that can be expected between test results when the method is used in one or more competent laboratories. The present study aims to enhance the precision statements in ASTM standards pertaining to the geometric, material, mechanical, and physical properties required for GFRP bars in concrete reinforcement, including ASTM standards like ASTM D7205M-21, Standard Test Method for Tensile Properties of Fiber Reinforced Polymer Matrix Composite Bars; ASTM D7617M-11(2017), Standard Test Method for Transverse Shear Strength of Fiber-Reinforced Polymer Matrix Composite Bars; and ASTM D7913M-14(2020), Standard Test Method for Bond Strength of Fiber-Reinforced Polymer Matrix Composite Bars to Concrete by Pullout Testing, while in accordance with the statistical procedures and calculation methods outlined in ASTM Practices ASTM E177-20, Standard Practice for Use of the Terms Precision and Bias in ASTM Test Methods, and ASTM E691-22, Standard Practice for Conducting an Interlaboratory Study to Determine the Precision of a Test Method. 

The main protease (M pro ) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an attractive target for antiviral therapeutics. Recently, many high-resolution apo and inhibitor-bound structures of M pro , a cysteine protease, have been determined, facilitating structure-based drug design. M pro plays a central role in the viral life cycle by catalyzing the cleavage of SARS-CoV-2 polyproteins. In addition to the catalytic dyad His41–Cys145, M pro contains multiple histidines including His163, His164, and His172. The protonation states of these histidines and the catalytic nucleophile Cys145 have been debated in previous studies of SARS-CoV M pro , but have yet to be investigated for SARS-CoV-2. In this work we have used molecular dynamics simulations to determine the structural stability of SARS-CoV-2 M pro as a function of the protonation assignments for these residues. We simulated both the apo and inhibitor-bound enzyme and found that the conformational stability of the binding site, bound inhibitors, and the hydrogen bond networks of M pro are highly sensitive to these assignments. Additionally, the two inhibitors studied, the peptidomimetic N3 and an α-ketoamide, display distinct His41/His164 protonation-state-dependent stabilities. While the apo and the N3-bound systems favored N δ (HD) and N ϵ (HE) protonation of His41 and His164, respectively, the α-ketoamide was not stably bound in this state. Our results illustrate the importance of using appropriate histidine protonation states to accurately model the structure and dynamics of SARS-CoV-2 M pro in both the apo and inhibitor-bound states, a necessary prerequisite for drug-design efforts.