Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.

The present invention is the use of purine nucleotide phosphoramidates or pharmaceutically acceptable salts thereof administered in an effective amount for the treatment or prevention of COVID-19, an infection caused by the SARS CoV-2 virus in a host, for example a human, in need thereof.

The present invention is the use of purine nucleotide phosphoramidates or pharmaceutically acceptable salts thereof administered in an effective amount for the treatment or prevention of COVID-19, an infection caused by the SARS CoV-2 virus in a host, for example a human, in need thereof.

The present disclosure provides the dinucleotide compounds which is useful for treating various cancers. The present disclosure also provides a composition comprising the compound or its pharmaceutically acceptable salt. The present disclosure also provides a medical use of the compound, its salt or the composition comprising the compound or its pharmaceutically acceptable salt for treating cancer. The present disclosure also provides a method of treatment of cancer comprising administering the compound, its salt or the composition comprising the compound or its salt to a subject in need of such treatment.

Reaction mixtures are provided having at least a first nucleotide analog and a second nucleotide analog that produce signals in response to excitation illumination. The signals produced by the analogs have peaks at the same wavelengths, but have distinct signal intensities. The distinct intensities allow for identification of the analogs in nucleic acid sequencing. In some embodiments, FRET-labeled compounds are provided. In certain embodiments, FRET-labeled nucleotide analogs are used, for example, in DNA sequencing or RNA sequencing.

Reaction mixtures are provided having at least a first nucleotide analog and a second nucleotide analog that produce signals in response to excitation illumination. The signals produced by the analogs have peaks at the same wavelengths, but have distinct signal intensities. The distinct intensities allow for identification of the analogs in nucleic acid sequencing. In some embodiments, FRET-labeled compounds are provided. In certain embodiments, FRET-labeled nucleotide analogs are used, for example, in DNA sequencing or RNA sequencing.

The present invention is a process for the preparation of certain 5′-phosphoramidate nucleotide diastereoisomers. The phosphoramidates include those useful in the treatment of cancer such as NUC-3373 (5-fluoro-2′-deoxyuridine-5′-O-[1-naphthyl(benzyloxy-L-alaninyl)]phosphate).

The present invention is a process for the preparation of certain 5′-phosphoramidate nucleotide diastereoisomers. The phosphoramidates include those useful in the treatment of cancer such as NUC-3373 (5-fluoro-2′-deoxyuridine-5′-O-[1-naphthyl(benzyloxy-L-alaninyl)]phosphate).

Compounds useful for forming nucleic acids having the structure of Formula I:

##STR00001##

Each of R.sup.1 or R.sup.2 is independently selected from hydrogen, a protecting group, or a phosphoramidite group. R.sup.3 is selected from H, F, O—C.sub.1-6 alkyl, O-MOE and a removable hydroxyl-protecting group. Q is a heterocyclic base. R.sup.4 is a cyclic hydrocarbon. Also disclosed are processes for forming the nucleic acids from the compounds and the nucleic acid products produced.

Compounds useful for forming nucleic acids having the structure of Formula I:

##STR00001##

Each of R.sup.1 or R.sup.2 is independently selected from hydrogen, a protecting group, or a phosphoramidite group. R.sup.3 is selected from H, F, O—C.sub.1-6 alkyl, O-MOE and a removable hydroxyl-protecting group. Q is a heterocyclic base. R.sup.4 is a cyclic hydrocarbon. Also disclosed are processes for forming the nucleic acids from the compounds and the nucleic acid products produced.