Remdesivir (RDV) has garnered much hope for its moderate anti-COVID-19 effects, but its limited amelioration of survival in hospitalized patient causes a huge controversy over the applicability of RDV to COVID-19 treatment. Developing strategies to improve its antivirus efficacy is urgently required. As anticipated, RDV exhibits similar behavior with other nucleotide analogs to disrupt the metabolism of natural endogenous ribonucleotides (RNs) and deoxyribonucleotides (dRNs). Alterations in endogenous RNs and dRNs play a critical role in virus replication as well as other key cellular functions. Thus elucidation of the disturbances of RDV on RNs and dRNs could help to understand its exact mechanism of action. Here, the metabolic profiling determined by liquid chromatography–mass spectrometry method showed a general increase in the abundance of nucleotides and a more than 2-fold increase for specific nucleotides. However, the variation of pyrimidine ribonucleotides was relative slight or even contrary, resulting in obvious imbalance between purine and pyrimidine ribonucleotides, which implied the obstacle of RDV to pyrimidine synthesis and could further block the transcription and replication of viral RNA. Additionally, the extreme disequilibrium between cytidine triphosphate (CTP) and cytidine monophosphate might result from the inhibition of CTP synthase and provide a metabolic target for the treatment of COVID-19 infection. Since nucleotides metabolism pathways are vulnerable to nucleotide analogues and are liable to be the regulation targets, it is promising to enhance the efficacy of RDV through co-administration with CTP synthase inhibitors or de novo pyrimidine synthesis inhibitors to exacerbate the imbalance of nucleotide pools.

The time symmetry of T_c = CT is redefined based on the 4-D Euclidean space. The time inversion symmetry of T_c = CT changes the signs of the charge (q) and absolute time (ct) of the particle. The P symmetry changes the signs of the space momenta and handedness of the particle. The T_c symmetry changes the signs of the time momentum (P_t=E/c) and charges. The handedness are classified as the left-handedness and right-handedness on the 3-D space. The charges (|q| = cDt) and energies (E= cDtDV) of the particles are originated from the upward warping (q>0) and downward warping (q<0) of the particles along the time axis. The evolution of our matter universe with P_t > 0 since the big bang can be interpreted based on the CTP symmetry with the partner antimatter universe with p_t < 0. The photon space is called as the vacuum space. Then the E and M waves are the space fluctuations, and the gravitational G wave is the time fluctuations. And the E, M and G fields are newly explained. The zero E and M fields of the photon space indicates that the photon space and gamma ray are the 2EM waves. The rest mass energy of the particle is the 4-D space volume of the warped photon space. In the present work, the quantum wave function is considered as the 4-D vector with the space wave function and time axis wave function in the 4-D Euclidean space. The warped photon space corresponds to the squared wave function which is the probability density. It is concluded that, in the quantum mechanics, the imaginary number concept is introduced in the quantum wave functions instead of the time axis component of the 4-D wave function vector. The left-handed neutrino puzzle is explained from the handedness partner relation with the right-handed dark matters. Finally, the modified Lorentz transformations derived in the 4-D Euclidean space are compared with the Lorentz transformations of the special and general relativity theories in the 4-D Minkowski space.